Encapsulation Using Hyperbranched Polymers: From Research and

Ind. Eng. Chem. Res. 2010, 49, 1169–1196

1169

Encapsulation Using Hyperbranched Polymers: From Research and Technologies to Emerging Applications Muhammad Irfan and Matthias Seiler* EVonik Degussa GmbH, Process Technology & Engineering, Rodenbacher Chaussee 4, D-63457 Hanau, Germany

Dendritic macromolecules, such as hyperbranched polymers are increasingly being studied in the context of encapsulation. The intensive research on encapsulation using hyperbranched polymers is motivated by factors such as a cost-effective polymer synthesis and a customizable property profile. Hence, in the past few years, hyperbranched polymers have been employed as carriers for several guest molecules such as dyes, pharmaceuticals, cosmetics, catalysts, and aromatic hydrocarbons. However, hyperbranched polymers compete not only with perfectly structured dendrimers but also with conventional carrier molecules in terms of price and performance criteria such as processability, loading capacity, delivery efficiency and/or reduction of toxic side effects. This article aims at reviewing the research and development (R&D) in the field of encapsulation using hyperbranched polymers. Based on a summary of the most relevant R&D results and encapsulation technologies in this area, progress and challenges are discussed and new emerging applications are described. The most prominent emerging applications include the encapsulation and/or controlled release of (i) unstable or sensitive components (such as those used in the field of personal care), (ii) pharmaceutical substances (using hyperbranched carrier polymers with a narrow molar mass distribution), and (iii) inorganic nanoparticles to design versatile nanoreactors for catalytic applications. 1. Hyperbranched Polymers About 50 years after the introduction of the “macromolecular hypothesis” by Staudinger, the entire field of polymer science could be described as consisting of only two major architectural classes: (i) linear topologies, such as those found in thermoplastics, and (ii) cross-linked architectures, such as those found in thermosets.1 Now, at the beginning of the 21st century, four major domains can be defined and distinguished in accordance with their properties and architecture: (I) Linear, random coil thermoplastics, such as plexiglass or nylon, (II) Cross-linked thermosets, such as epoxy resins, (III) Branched systems based on long-chain branching in polyolefins, such as low-density poly(ethylene) and other related branched topologies, (IV) Dendritic polymers consisting of three subsets that are based on the degree of structural control, namely (a) random hyperbranched polymers, (b) dendrigraft polymers, and (c) dendrimers. Because of the unique repertoire of new properties, dendritic polymers are recognized as a fourth major architectural class:1 this is a class with a young but well-established body of interdisciplinary research exploring a remarkable variety of potential applications. The tedious and complex multistep synthesis of dendrimers results in expensive products with limited use for large-scale industrial applications. For many applications, which do not require structural perfection, using hyperbranched polymers can circumvent this major drawback of dendrimers. Unlike dendrimers, randomly branched hyperbranched polymers with almost similar properties can be easily synthesized via onestep synthesis and, therefore, also represent economically promising products for large-scale industrial applications.2 * To whom correspondence should be addressed. Tel.: +49 6181593049. Fax: +49 61815973049. E-mail: matthias.seiler@ evonik.com.

Most of the applications of hyperbranched polymers are based on the absence of chain entanglements, the globular shape, and/ or the nature and the large number of functional groups within a molecule. Modification of the number and type of functional groups of hyperbranched polymers is essential to control their solubility, compatibility, reactivity, adhesion to various surfaces, self-assembly, chemical recognition, as well as electrochemical and luminescence properties. In other words, the large number of functional groups allows customizing their thermal, rheological, and solution properties and thus provides a powerful tool to design hyperbranched polymers for a wide variety of applications. 1.1. Synthesis. Hyperbranched polymers and dendrimers share a few common features, such as their preparation from ABx monomers, which leads to highly branched macromolecules with a large number of functional end groups. However, the synthetic approaches for hyperbranched polymers and dendrimers differ substantially; hence, differences in molecular shape, architecture, and, often, properties are observed. Hyperbranched polymers are prepared in one-step procedures, most common via the polycondensation of ABx monomers.3,4 If x g 2 and the functionality A reacts only with functionality B of another molecule, the polymerization of ABx monomers results in highly branched polymers.4 Apart from polycondensation, addition polymerization of monomers containing an initiating function and a propagating function in the same molecule,5 ring-opening polymerization6 and self-condensing Vinyl polymerization (SCVP)7 also can be applied for the synthesis of hyperbranched macromolecules.5 The copolymerization of A2 and B3 monomers represents an alternative method for the preparation of hyperbranched polymers.8-11 However, the polymerization of A2 and B3 monomers generally leads not only to branching but also to cross-linking reactions that might cause gelling. Therefore, many studies have focused on the investigation of the optimum polymerization conditions. For example, Jikei et al. suggested a polycondensation approach to synthesize hyperbranched polymers from bifunctional (A2) and

10.1021/ie900216r  2010 American Chemical Society Published on Web 01/04/2010

1170

Ind. Eng. Chem. Res., Vol. 49, No. 3, 2010

Figure 1. A hyperbranched polymer, with its different segment types, from the polymerization of AB2 monomers.13

trifunctional (B3) monomers. In this synthetic approach, the condensation step of A2 and B3 molecules (such as aromatic diamines as A2 and aromatic trimesic acids as B3 molecules) was performed faster than the propagation step. The fast condensation of A2 and B3 accumulated AB2 molecules as intermediate monomers that led to hyperbranched aromatic polyamides. Hence, a direct reaction to synthesize hyperbranched polymers from A2 and B3 monomers occurs.9 In another example, hyperbranched poly(aryl ester)s were synthesized by adding the diluted solution of bisphenol A (A2) into the diluted solution of 1,3,5-benzenetricarbonyl trichloride (B3). It was observed that the order of solution addition (i.e., A2 into B3) and solution concentrations require careful evaluation to avoid gelation.10 By now, several excellent reviews on the synthetic approaches for hyperbranched polymers have been published (see the reviews mentioned later in this paper in Table 1) that give detailed insight into the underlying methodologies and reaction mechanisms. The one-step procedures used for the preparation of hyperbranched polymers lead to uncontrolled random growth. Consequently, the resulting structures are imperfect and polydisperse. Furthermore, unlike dendrimers, the control over layers or generations, as well as over the molar mass deteriorates. Because of the statistical nature of the coupling steps, steric hindrance of growing chains, and reactivity of functional groups, the propagation occurs at only two of the branching units, which gives different polymer segments.12 The different segment types within a hyperbranched macromolecule are depicted in Figure 1. Based on AB2 monomers, linear segments, known as defects, show one functional B-group unreacted, whereas the terminal segments have two unreacted B-functionalities (recall Figure 1). Similar to dendrimers, the dendritic segments in hyperbranched macromolecules represent fully incorporated monomers that do not have any unreacted functionalities. The most prominent feature of hyperbranched polymers is their “degree of branching” (DB). This term defines the ratio of branched, terminal, and linear units within the macromolecular structure. Further information on the degree of branching can be found elsewhere.14-18 (Abbreviations are explained in a separate section at the end of this paper.) 1.2. Properties. Thermal Properties. Because of their highly branched structure, dendritic polymers are almost exclusively amorphous materials. Therefore, the glass-transition temperature (Tg) is one of the most important thermal properties. Tg is an important parameter for a dendritic polymer, with respect to potential applications in the field of powder coatings, rheology modifiers, or encapsulation. Upon heating, amorphous

components convert at Tg from a glassy state to a liquid state, i.e., into a melt for low-molar-mass substances or a rubbery state for high-molar-mass compounds. In the melt, thermal energy is sufficiently high for long segments of each polymer chain to move in random micro-Brownian motions. In the amorphous solid state, on the other hand, polymer chains assume their unperturbed dimensions as they do in solution under theta conditions. Below Tg, all long-range segmental motions cease. Rotations around single bonds become very difficult and the only molecular motions that can occur are short-range motions of several contiguous chain segments and motions of substituent groups.19 In the case of dendritic polymers, the situation is more complex, because segmental motions are also affected by the branching points and the presence of numerous functional groups. The Tg value of a hyperbranched polymer is not only affected by the chain-end composition, but also by the molar mass and the macromolecular composition.20 According to Schmaljohann et al., it can be understood as a combination of intermolecular and intramolecular effects. Differences in Tg of hyperbranched polymers with different repeating units but the same end groups demonstrate the intramolecular effect of segmental motion, whereas the change of Tg through variation of the end groups (their polarity in particular) can be assigned to translational motion and an intermolecular effect.21 For dendritic polymer systems, Tg increases with the generation number to a limit, above which it remains almost constant.20 This increase in Tg with the generation number is assumed to reflect a decrease in chain mobility due to branching. Many research groups have demonstrated that the chemical nature of the large number of terminal groups strongly affects Tg.15,20-30 By means of DSC measurements, Sunder et al. demonstrated that the flexibility (i.e., Tg) of a modified highly polar hyperbranched polymer with large number of hydroxyl end groups is controlled mainly by two factors: (i) hydrogen bonding of the end groups, increasing the rigidity of the molecules, and (ii) tendencies of the substituents to form higher-ordered phases (mesophases, crystallization).27 It is important to know that the degree of alkyl substitution has hardly any effect on the melting temperature (Tm); however, there is a pronounced effect on Tg.27 Further information on the thermal properties of hyperbranched polymers can be found elsewhere.15,21,23,27-30 Mechanical and Rheological Properties. Investigations on new applications of a polymer are often closely related to its material and processing properties. Therefore, the mechanical and rheological properties of hyperbranched polymers are very important. Because of the highly branched, globular structure, the configuration of hyperbranched polymers and dendrimers is coined by a lack of chain entanglements.31 The nonentangled state imposes poor mechanical properties, resulting in brittle dendritic polymers with limited use as thermoplastics.24 The stress-strain behavior of hyperbranched polymers can be considered similar to that of ductile metals for hyperbranched polyesters.28 Similar to ductile metals, hyperbranched polyesters do not strain-harden. This is due to their globular structure, which does not permit the process of chain extension and orientation (the usual mechanisms of strain hardening). However, intermolecular associations, such as hydrogen bonding and possibly intermolecular crystallization of a few linear segments, provide connections between the hyperbranched macromolecules.28


Figure 2. Generalized description of the viscosity behavior of dendrimers, hyperbranched and linear polymers as a function of molar mass: (a) melt viscosity versus molar mass52 and (b) intrinsic viscosity versus molar mass.55

Apart from the mechanical properties, the viscosity behavior of linear and branched polymers also shows remarkable differences. This was already noted by several scientists at the end of the 1960s.32-37 Unlike linear polymers, the globular, highly branched architecture of both hyperbranched polymers and dendrimers prevents chain entanglements, resulting in considerably smaller melt viscosities and a continuous slope of the η-function. There are several studies confirming the strikingly low melt viscosities of dendritic polymers, in comparison to linear polymers.5,24,26,38-44 Analyzing the melt viscosity behavior depicted in Figure 2a, for linear polymers, a dramatic increase in viscosity is observed after a critical molar mass. However, the line for dendritic polymers (such as polyether dendrimers) shows a continuous slope of 1.1, up to 100 000 amu with no critical weight limit being observed. This behavior can be explained by the different macromolecular structure of linear and dendritic macromolecules. For low molar masses, linear polymers consist of random coil chains which, as the molar mass increases, start to entangle at a critical molecular size, leading to a sharp increase in melt viscosity. However, the viscosity of hyperbranched polymers with low molar masses (Mn < 5000 g/mol) is attributed to the solution conformation, not to the lack of entanglements.45 Unlike hyperbranched polymers, the globular, highly branched architecture of dendrimers seems to prevent chain entanglements, resulting in a continuous slope of melt viscosity. Similar results were found for hyperbranched polymers.5 Kim concluded that the properties of dendritic polymers were dependent more on the chain length between the branching points than on the total molar mass. Therefore, regardless of the total molar mass, a highly branched polymer behaves like a low-molecular-mass polymer, as long as the chain length between the branching points is less than the critical molecular mass for chain entanglements.5

1171

Furthermore, the melt behavior of dendritic macromolecules is expected to be greatly affected by the nature of the functional end groups. For instance, Ihre et al. demonstrated that, in the case of different aliphatic hyperbranched polyesters, an increase in end group polarity can increase the dynamic viscosity by several orders of magnitude.46 Hsieh et al. rheologically characterized a series of commercially available aliphatic hyperbranched polyesterssBoltorn polymers47sin the molten state. Boltorn polymers of lower generations (Mw ) 2100-3500 g/mol) exhibit comparatively short linear viscoelastic regions, which generally are only observed for microstructured materials such as liquid crystalline polymers and suspensions.48 Moreover, the storage moduli of these hyperbranched polyesters are very close to their loss moduli, whereas the loss moduli of the highergeneration polymers (Mw ) 5100-7500 g/mol) are much greater than their storage moduli.48 Also, shear-thinning behavior in oscillatory and steady shear was observed for the lowergeneration polymers, which does not correspond to Newtonian behavior.48 Hence, it can be concluded that melt viscosities of hyperbranched polymers significantly differ from that of linear polymers, because of structural differences and a lack of chain entanglements. Moreover, the dynamic viscosity of hyperbranched polymers is dependent on the functional end groups. Further details concerning the melt viscosity of hyperbranched polymers can be found in the literature.5,23,24,26,38-44,49-51 Solution Properties. Many research studies have been published focusing on dilute and semidilute properties of branched polymer systems.40,45,52-64 Hyperbranched polymers have a significantly lower intrinsic viscosity, Mark-Houwink exponent, hydrodynamic volume, and ratio of radius of gyration to hydrodynamic radius in comparison to their linear analogues of the same molar mass.39 The intrinsic viscosity (η) is directly related to the hydrodynamic dimensions of macromolecules at infinite dilution and only indirectly to the molar mass because of well-defined relationships between hydrodynamic volumes and molar masses for polymers of identical shapes and segment distributions.65 The dependence of the intrinsic viscosity on the molar mass can be described by the empirical Kuhn-Mark-HouwinkSakurada (KMHS) equation, η ) KηMaη where Κη and aη are system-specific constants that are dependent on the constitution, configuration, and molar mass distribution of the polymer, as well as being dependent on the solvent power and the system conditions. The Fox-Flory equation, ΦRg3 η) M connects the intrinsic viscosity η with the radius of gyration Rg. The front factor (Φ) is dominated by hydrodynamic interactions and, thus, by the segment density. The segment density is larger for branched macromolecules than for linear polymer coils. Therefore, with an increasing degree of polymer branching, an increase in Φ can be expected, while, at the same time, Rg decreases, because of contraction of the molecule.53 The intrinsic viscosity of hyperbranched polymers does not change linearly with generation number.40,53,55-57,66,67 Also, hyperbranched polyesters such as the commercially available Boltorn series do not show a maximum in η with increasing molar mass.57,67 Investigations of their hydrodynamic volume demonstrated the high flexibility of the Boltorn polymers in solution. Depending on the solvent, the hydrodynamic volume

1172


Figure 3. Proposed applications of hyperbranched polymers.

of the hyperbranched Boltorn polyesters can change by a factor of 2, allowing for cores with a free volume of ∼0.95 nm3 and the capability of hosting a molecule with a radius of 0.61 nm.57 Further dilute solution aspects of hyperbranched polyesters are discussed elsewhere.54 For randomly branched macromolecules, KMHS exponents of aη < 0.4 have been determined.53,54 (Theory predicts values of aη ) 0 for spheres, aη ) 0.5 for unperturbed coils in theta solvents, aη ) 0.764 for perturbed coils in good solvents, and aη ) 2 for infinitely thin, rigid rods.65) Also, the ratio radius of gyration to hydrodynamic radius (Rg/Rh), which is a sensitive fingerprint of the inner density profile of macromolecules, differs between hyperbranched and linear polymers. For hyperbranched polymers, the values of Rg/Rh are in the range of 0.82-0.89 (for hyperbranched copolymers in the range of 0.76-1.41,68), whereas, for linear unperturbed polymers and hard spheres of uniform density, values of 1.25-1.37 are observed.58 The η values of hyperbranched copolymers increases gradually with increasing molar mass, similar to those obtained for other hyperbranched polymers.59 Alternating hyperbranched copolymers show a ratio of Rg/Rh ) 0.79-0.83 and seem to behave similar to hard spheres in dilute solutions.59 Within the architectural class of dendritic polymers, the investigated intrinsic viscosities of hyperbranched polymers52,69-71 and dendrimers31,40,72-75 have been compared with each other and with linear polymers.23,52 It has been observed that the difference in molecular shapes of dendrimers, as well as hyperbranched and linear polymers, lead to remarkable deviations in the intrinsic viscosity. Figure 2b compares the intrinsic viscosity versus molar mass (η vs M) relationship for hyperbranched polyesters, convergent polyether dendrimers, and linear polystyrenes. It can be seen that dendrimers show a totally unique bell-shaped relationship with a maximum below 5000 amu.52,76 This observation does not obey standard theory, whereas the intrinsic viscosity of hyperbranched and linear polymers increases according to the KMHS equation, although, in case of hyperbranched polymers, the constant R is comparatively low. Hawker and Devonport76 explain this behavior with

the globular, almost spherical structure of dendrimers, resulting in an increase in volume, according to V ) 4πr3/3, while a dendrimers’ mass doubles at each generation and, thus, increases exponentially in accordance with Mw ≈ 2(generation-1). Up to high molar masses, the rheology behavior of dendrimers is dominated not by interchain entanglements, but by interdigitation or interpenetration of the globular macromolecules, which leads to the direct proportionality between intrinsic viscosity η and viscosity-average molar mass Mη.77 On the other hand, hyperbranched polymers carry their functional groups both at the chain ends and throughout the molecule. The hyperbranched structure is more elongated than spherical because their growth is a kinetic process affected by steric inhibitions. Therefore, hyperbranched polymers may offer less hindered access to their single “A” group, as compared to a high-generation dendrimer having a focal point.52 It can be concluded that hyperbranched polymers have a significantly lower intrinsic viscosity, a smaller Mark-Houwink exponent (aη), and also a lower hydrodynamic volume, as compared to their linear analogues of the same total molar mass.45 Hence, Kharchenko et al. suggested to perceive hyperbranched polymers as compact soft-sphere-like structures. For many potential applications of hyperbranched polymers in the field of encapsulation, the thermodynamics of concentrated hyperbranched polymer solutions is also of great importance. This area has been previously reviewed13,39,78 and will be considered in section 3. 1.3. Applications. Over the past 10 years, hyperbranched polymers have been suggested for a wide variety of applications (see Figure 3). However, only a few of them succeeded in overcoming the market entry barriers.2 Perstorp demonstrated that hyperbranched aliphatic polyols can be used, for example, for hardcoat applications, because they allow for a unique combination of coating properties such as high hardness, scratch resistance, and flexibility while ensuring at the same time low viscosity and low shrinkage.79 Evonik Degussa uses hyperbranched polymers as performance

Ind. Eng. Chem. Res., Vol. 49, No. 3, 2010 Table 1. Selected Reviews on Hyperbranched Polymers reference source

year

synthesis

properties

Kim5 Frećhet and Hawker52 Hult et al.24 Voit22 Jikei and Kakimoto82 Seiler227 Frey and Haag84 Yates et al.85 Gao and Yan86 Voit23 Seiler13

1998 1996 1999 2000 2001 2002 2002 2004 2004 2005 2006

× × × × ×

× × ×

× × ×

× × × × × × ×

applications

Table 2. Physical, Chemical, and High Pressure Encapsulation Processes physical processes

× × × × × × × × ×

additives and enzymatically degradable carriers.2 DSM introduced hyperbranched polyesteramides to oil field applications, because of their ability to suppress the crystallization of gas hydrates from water-hydrocarbon mixtures.80 And BASF demonstrated that hyperbranched polymers can be used, for example, as cross-linkers for coatings and several adjacent markets.81 As summarized by the reviews listed in Table 1 (also see references therein), a large number of research groups investigated structure-property relationships and additional applications of hyperbranched polymers. In this context, very promising and fascinating investigations have been carried out with respect to encapsulation issues involving hyperbranched polymers. To highlight the potential of this new emerging area, this article intends to review for the first time the most relevant research contributions and to discuss opportunities and remaining challenges. 2. Encapsulation The encapsulation phenomenon refers to the incorporation of an active substance in a shell or a matrix of a carrier component.87 “Active substance” is a term used to describe pharmaceutically, biologically, catalytically, chemically, or surface active substances.87-89 The encapsulation of such an active substance taking place at the micrometer or submicrometer scale is referred to as microencapsulation or nanoencapsulation, respectively.87 The term “microsphere” is used for spheres 1-1000 µm in size. Ideally, microspheres are completely spherical and monodisperse, although spheres with a size distribution are also often referred to as microspheres/nanospheres.90 Unlike the term microparticle/nanoparticle, the term microspheres applies to colloids and micelles as well. In context of microencapsulated/nanoencapsulated assemblies, the term microsphere is employed for both, core-shell and matrix morphologies.91,92 The submicrometer encapsulation of an active substance in the cavities of a macromolecule is called “molecular encapsulation” and the macromolecule is referred to as a “nanocarrier”.93 Such macromolecular assemblies that contain active substances are also termed “nanocapsules”.94 In this review, the term “nanocapsule” is used for both nanoencapsulated active substances and molecularly encapsulated guest molecules. The history of microencapsulation87,95-97 dates back to the 1940s, when the spray-coating technique was commercially developed to preserve scarce food.98 Green et al.99 demonstrated the encapsulation of ink droplets by a phase separation method, which was called “coacervation”. The development of the coacervation method proved to be a milestone in the field of microencapsulation, because it allowed for a reproducible particle size of 50 wt %), compared to the encapsulation technologies that produce matrix-structured assemblies.87,96,98-100,105,106,109,114 The core-shell structured microparticles/nanoparticles essentially consist of a “core” (active ingredient) and a “shell” (carrier substance). Principally, the carrier substance is deposited over the active ingredient in the shape of a film that forms a “shell” upon stabilization. The thickness of the carrier substance film is dependent on the processing parameters (such as operating temperature, pressure, concentrations, etc.), carrier properties (such as viscosity, molar mass, melting point, etc.), and interactions between the active ingredient and carrier substance.87,96,98,105,106,109,114 The shell thickness corresponds to the amount of the carrier substance in the formulation, which, in turn, determines the payload in the formulation. Hence, the control over the process parameters and a careful evaluation of the carrier properties helps in optimizing the loading capacity of a formulation. Most physical encapsulation technologies such as spray coating, fluidized-bed coating, or pan coating can give a loading capacity as high as 99 wt %, albeit the risk of incomplete coating.98,105,107,117,151 Chemical encapsulation technologies such as simple/complex coacervation, solvent evaporation or emulsion polymerization are best-suited for microparticles 3 and show side effects, in terms of toxicity, that limit their application in the field of polymer therapeutics. Although fundamental studies have been performed and excellent results underlining the versatility of hyperbranched polymers have been published, further research is necessary in most of the areas discussed, to provide a solid comparison with established state-of-the-art carriers and to overcome the market entry barriers. With regard to the identified challenges discussed in this review, the following aspects can be considered to be crucial for leveraging the full potential of innovative encapsulation approaches using hyperbranched polymers: (i) demonstrating the superiority of hyperbranched carriers over conventional carrier polymers in terms of price/performance ratio, (ii) providing solvent-free active formulations with a task-specific stability, and (iii) making biodegradable, nontoxic hyperbranched polymers with a narrow molar mass distribution and a defined architecture commercially available.

Acknowledgment The authors would like to thank Prof. Wolfgang Arlt (Friedrich-Alexander-University, Erlangen-Nuremberg, Germany) and Prof. John M. Prausnitz (University of California, Berkeley, CA) for scientific guidance. Thanks also to Prof. Irina Smirnova (Technical University Hamburg-Harburg, Germany) for valuable discussions. Furthermore, we would like to acknowledge the continuous encouragement and support of Dr. Axel Kobus and Prof. Ulf Plo¨cker (Evonik Degussa GmbH). Abbreviations Ahx ) aminohexanoic acid amu ) atomic mass unit API ) active pharmaceutical ingredient ATRP ) atom transfer radical polymerization AY ) Alizarin Yellow BAS ) biologically active substance CLPAE ) cross-linked poly(β-amino ester) CMC ) critical micelle concentration CR ) Congo Red DMAP ) 4-(dimethylamino)-pyridine DMF ) N,N-dimethylformamide DM ) D-mannan DB ) degree of branching ELM ) emulsion liquid membranes EY ) Eosin Y FS ) Fluorescein Sodium GAS ) gas antisolvent method 1 H NMR ) proton nuclear magnetic resonance spectroscopy LA/NHn ) lactide/amino functional group ratio LLEE ) L-leucine ethyl ester Mn ) number-averaged molar mass MO ) Methyl Orange MTT ) 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide O/W ) oil-in-water (emulsion) PAE ) poly(amino ester) PAH ) polycyclic aromatic hydrocarbons PAMAM ) poly(amido amine) PBLG ) poly(g-benzyl L-glutamate) PDMA ) poly(N,N-dimethylaminoethyl methacrylate) pDNA ) plasmid DNA PDI ) polydispersity index PEA ) poly(ester amine) PEG ) poly(ethylene glycol) PEI ) polyethylenimine PEO ) poly(ethylene oxide) PG ) polyglycerol PGSS ) particles from gas saturated solutions PHEMA ) poly(2-hydroxyethyl methacrylate) PLA ) poly(lactide) PLGA ) poly(lactide-co-glycolide) PLLA ) poly(L-lactide) Polyplex ) polymer complex PY ) pyrene RB ) Rose Bengal RESS ) rapid expansion of supercritical solvents R&D ) research and development RG ) Rhodamine 6G SEC ) size exclusion chromatography siRNA ) small interfering ribonucleic acid TC ) transport capacity VPO ) vapor pressure osmometry


Literature Cited (1) Frećhet, J. M. J.; Tomalia, D. A. Dendrimers and Other Dendritic Polymers; John Wiley & Sons: New York, 2001. (2) Seiler, M. Hyperbranched Polymers: Multitalented Individualists. In Evonik Science Letter; Hanau, Germany, 2008; pp 12-17. (3) Kim, Y. H.; Webster, O. W. Water Soluble Hyperbranched Polyphenylene: A Unimolecular Micelle? J. Am. Chem. Soc. 1990, 112, 4592. (4) Flory, P. J. Principles of Polymer Chemistry; Cornell University Press: London, 1953. (5) Kim, Y. H. Hyperbranched Polymers 10 Years After. J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 1685. (6) Sunder, A.; Hanselmann, R.; Frey, H.; Mu¨lhaupt, R. Controlled Synthesis of Hyperbranched Polyglycerols by Ring-Opening Multibranching Polymerization. Macromolecules 1999, 32, 4240. (7) Frećhet, J. M. J.; Henmi, M.; Gitsov, I.; Aoshima, S.; Leduc, M. R.; Grubbs, R. B. Self-Condensing Vinyl PolymerizationsAn Approach to Dendritic Materials. Science 1995, 269, 1080. (8) Emrick, T.; Chang, H. T.; Frećhet, J. M. J. An A2 + B3 Approach to Hyperbranched Aliphatic Polyethers Containing Chain End Epoxy Substituents. Macromolecules 1999, 32, 6380. (9) Jikei, M.; Chon, S. H.; Kakimoto, M. A.; Kawauchi, S.; Imase, T.; Watanebe, J. Synthesis of Hyperbranched Aromatic Polyamide From Aromatic Diamines and Trimesic Acid. Macromolecules 1999, 32, 2061. (10) Lin, Q.; Long, T. E. Polymerization of A2 with B3 Monomers: A Facile Approach to Hyperbranched Poly(aryl ester)s. Macromolecules 2003, 36, 9809. (11) Hao, J.; Jikei, M.; Kakimoto, M. Synthesis and Comparison of Hyperbranched Aromatic Polyimides Having the Same Repeating Unit by AB2 Self-Polymerization and A2+ B3 Polymerization. Macromolecules 2003, 36, 3519. (12) Inoue, K. Functional Dendrimers, Hyperbranched and Star Polymers. Prog. Polym. Sci. 2000, 25, 453. (13) Seiler, M. Hyperbranched Polymers: Phase Behavior and New Applications in the Field of Chemical Engineering. Fluid Phase Equilib. 2006, 241, 155. (14) Ho¨lter, D.; Burgath, A.; Frey, H. Degree of Branching in Hyperbranched Polymers. Acta Polym. 1997, 48, 30. (15) Magnusson, H.; Malmstro¨m, E.; Hult, A.; Johansson, M. The Effect of Degree of Branching on the Rheological and Thermal Properties of Hyperbranched Aliphatic Polyethers. Polymer 2002, 43, 301. (16) Radke, W.; Litvinenko, G.; Mu¨ller, A. H. E. Effect of core-forming molecules on molecular weight distribution and degree of branching in the synthesis of hyperbranched polymers. Macromolecules 1998, 31, 239. (17) Zˇagar, E.; Zˇigon, M. Characterization of a commercial hyperbranched aliphatic polyester based on 2,2-bis(methylol)propionic acid. Macromolecules 2002, 35, 9913. (18) Hawker, C. J.; Frećhet, J. M. J. One-step synthesis of hyperbranched dendritic polyesters. J. Am. Chem. Soc. 1991, 113, 4583. (19) Fried, J. R. Polymer Science and Technology; Prentice Hall PTR: Englewood Cliffs, NJ, 1995. (20) Wooley, K. L.; Hawker, C. J.; Pochan, J. M.; Frećhet, J. M. J. Physical Properties of Dendritic Macromolecules: A Study of Glass Transition Temperature. Macromolecules 1993, 26, 1514. (21) Schmaljohann, D.; Haüssler, L.; Po¨tschke, P.; Voit, B. I.; Loontjens, T. J. A. Modification With Alkyl Chains and the Influence on Thermal and Mechanical Properties of Aromatic Hyperbranched Polyesters. Macromol. Chem. Phys. 2000, 201, 49. (22) Voit, B. I. New Developments in Hyperbranched Polymers. J. Polym. Sci., Part A: Polym. Chem. 2000, 38, 2505. (23) Voit, B. I. Hyperbranched PolymerssAll Problems Solved After 15 Years of Research. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 2679. (24) Hult, A.; Johansson, M.; Malmstro¨m, E. Hyperbranched Polymers. AdV. Polym. Sci. 1999, 143, 1. (25) van Benthem, R. A. T. M. Novel Hyperbranched Resins for Coating Applications. Prog. Org. Coat. 2000, 40, 203. (26) Wooley, K. L.; Frećhet, J. M. J.; Hawker, C. J. Influence of Shape on the Reactivity and Properties of Dendritic, Hyperbranched and Linear Aromatic Polyesters. Polymer 1994, 35, 4489. (27) Sunder, A.; Heinemann, J.; Frey, H. Controlling the Growth of Polymer Trees: Concepts and Perspectives for Hyperbranched Polymers. Chem.sEur. J. 2000, 6, 2499. (28) Rogunova, M.; Lynch, T. Y. S.; Pretzer, W.; Kulzick, M.; Hiltner, A.; Baer, E. Solid-State Structure and Properties of Hyperbranched Polyols. J. Appl. Polym. Sci. 2000, 77, 1207. (29) Liu, Y. H.; Jing, X. L. Miscibility, Morphology, and Thermal Properties of Hyperbranched Polyborates Modified Phenolic Resins. J. Polym. Sci., Part B: Polym. Phys. 2008, 46, 2012.

1191

(30) Zhang, J.; Hu, C. P. Synthesis, Characterization and Mechanical Properties of Polyester-Based Aliphatic Polyurethane Elastomers Containing Hyperbranched Polyester Segments. Eur. Polym. J. 2008, 44, 3708. (31) Hawker, C. J.; Farrington, P. J.; Mackay, M. E.; Wooley, K. L.; Frećhet, J. M. J. Molecular Ball Bearings: The Unusual Melt Viscosity Behavior of Dendritic Macromolecules. J. Am. Chem. Soc. 1995, 117, 4409. (32) Graessley, W. W.; Masuda, T.; Roovers, J. E. L.; Hadjichristidis, N. Rheological Properties of Linear and Branched Polyisoprene. Macromolecules 1976, 9, 127. (33) Masuda, T.; Ohta, Y.; Onogi, S. Rheological Properties of Anionic Polystyrenes. III. Characterization and Rheological Properties of FourBranch Polystyrenes. Macromolecules 1971, 4, 763. (34) Mendelson, R. A.; Bowles, W. A.; Finger, F. L. Effect of Molecular Structure on Polyethylene Melt Rheology. I. Low-Shear Behavior. J. Polym. Sci., Part B: Polym. Phys. 1970, 8, 105. (35) Kraus, G.; Gruver, J. T. Thermal Expansion, Free Volume, and Molecular Mobility in a Carbon Black-Filled Elastomer. J. Polym. Sci., Part B: Polym. Phys. 1970, 8, 571. (36) Berry, G. C.; Fox, T. G. The Viscosity of Polymers and Their Concentrated Solutions. Fortschr. Hochpolym.-Forsch. 1968, 5, 262. (37) Fujimoto, T.; Narukawa, H.; Nagasawa, M. Viscoelastic Properties of Comb-Shaped Polystyrenes. Macromolecules 1970, 3, 57. (38) Le, T. C.; Todd, B. D.; Daivis, P. J.; Uhlherr, A. Rheology and Structural Properties of Hyperbranched Polymers: a Non-Equilibrium Molecular Dynamics Study. AIP Conf. Proc. 2008, 1027, 433. (39) Seiler, M. Phase Behavior and New Applications of Hyperbranched Polymers in the Field of Chemical Engineering, Ph.D. Dissertation (ISBN 3-18-382003-x),University of Erlangen-Nuremberg, Germany, 2004. (40) Mourey, T. H.; Turner, S. R.; Rubinstein, M.; Frećhet, J. M. J.; Hawker, C. J.; Wooley, K. L. Unique Behavior of Dendritic Macromolecules: Intrinsic Viscosity of Polyether Dendrimers. Macromolecules 1992, 25, 2401. (41) Pirrung, F. O. H.; Loen, E. M.; Noordam, A. Hyperbranched Polymers as a Novel Class of Pigment Dispersants. Macromol. Symp. 2002, 187, 683. (42) Bonacucina, G.; Ponchel, G.; Ringard, C.; Palmieri, G. F.; Grossiord, J. Rheological and Adhesive Properties of New Thermo-Responsive Hyperbranched Poly[Ethylene Oxide-b-Propylene Oxide-b-Ethylene Oxide]. J. Drug DeliVery Sci. Technol. 2006, 16, 59. (43) Oudshoorn, M. H. M.; Rissmann, R.; Bouwstra, J. A.; Hennink, W. E. Synthesis and Characterization of Hyperbranched Polyglycerol Hydrogels. Biomaterials 2006, 27, 5471. (44) Vukovic, J.; Lechner, M. D.; Jovanovic, S. Rheological Properties of Concentrated Solutions of Aliphatic Hyperbranched Polyesters. Macromol. Chem. Phys. 2007, 208, 2321. (45) Kharchenko, S. B.; Kannan, R. M.; Cernohous, J. J.; Venkataramani, S. Role of Architecture on the Conformation, Rheology, and Orientation Behavior of Linear, Star, and Hyperbranched Polymer Melts. 1. Synthesis and Molecular Characterization. Macromolecules 2003, 36, 399. (46) Ihre, H.; Johansson, M.; Malmstro¨m, E.; Hult, A. Dendrimers and Hyperbranched Aliphatic Polyesters Based on 2,2-Bis(Hydroxymethyl)Propionic Acid (Bis-MPA). AdV. Dendritic Macromol. 1996, 3, 1. (47) Hult, A. Polyester-Type Dendritic Macromolecules, and Their Manufacture and Use, Swedish Patent SE 468771. (48) Hsieh, T. T.; Tiu, C.; Simon, G. P. Miscibility of a Nematic Liquid Crystalline Polymer Pair. Polymer 2001, 42, 8007. (49) Monticelli, O.; Russo, S.; Campagna, R.; Voit, B. Preparation and Characterization of Blends Based on Polyamide 6 and Hyperbranched Aramids as Palladium Nanoparticle Supports. Polymer 2005, 46, 3597. (50) Lederer, A.; Voigt, D.; Appelhans, D.; Voit, B. Molar Mass Characterization and Solution Behaviour of Poly(ether amide) Dendrimers. Polym. Bull. (Heidelberg, Ger.) 2006, 57, 329. (51) Elrehim, M. A.; Voit, B.; Bruchmann, B.; Eichhorn, K. J.; Grundke, K.; Bellmann, C. Structural and End-Group Effects on Bulk and Surface Properties of Hyperbranched Poly(Urea Urethane)s. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 3376. (52) Frećhet, J. M. J.; Hawker, C. J.; Gitsov, I.; Leon, J. W. Dendrimers and Hyperbranched Polymers: Two Families of Three-Dimensional Macromolecules with Similar but Clearly Distinct Properties. J. Macromol. Sci.: Pure Appl. Chem. 1996, A33, 1399. (53) Burchard, W. Solution Properties of Branched Macromolecules. In Branched Polymers II; Springer: Berlin, 1999. (54) De Luca, E.; Richards, R. W. Molecular Characterization of a Hyperbranched Polyester. I. Dilute Solution Properties. J. Polym. Sci., Part B: Polym. Phys. 2003, 41, 1339. (55) Hawker, C. J.; Frećhet, J. M. J. Comparison of Linear, Hyperbranched, and Dendritic Macromolecules. ACS Symp. Ser. 1996 624, 132144.

1192


(56) Scherrenberg, R.; Coussens, B.; van Vliet, P.; Edouard, G.; Brackman, J.; de Brabander, E.; Mortensen, K. The Molecular Characteristics of Poly(propyleneimine) Dendrimers as Studied with Small-Angle Neutron Scattering, Viscosimetry, and Molecular Dynamics. Macromolecules 1998, 31, 456. (57) Mackay, M. E.; Carmezini, G. Manipulation of Hyperbranched Polymers’ Conformation. Chem. Mater. 2002, 14, 819. (58) Ishizu, K.; Mori, A. Solution Properties of Hyperbranched Polymers and Synthetic Application for Amphiphilic Star-Hyperbranched Copolymers by Grafting From Hyperbranched Macroinitiator. Polym. Int. 2002, 51, 50. (59) Ishizu, K.; Takashimizu, C.; Shibuya, T.; Uchida, S. Synthesis and Solution Properties of Alternating Maleimide/Styrene Hyperbranched Copolymers Via Controlled Radical Mechanism. Polym. Int. 2003, 52, 1010. (60) Striolo, A.; Prausnitz, J. M.; Bertucco, A.; Kee, R. A.; Gauthier, M. Dilute-Solution Properties of Arborescent Polystyrenes: Further Evidence for Perturbed-Hard-Sphere Behavior. Polymer 2001, 42, 2579. (61) Lue, L. Volumetric Behavior of Athermal Dendritic Polymers: Monte Carlo Simulation. Macromolecules 2000, 33, 2266. (62) Garamus, V. M.; Maksimova, T. V.; Kautz, H.; Barriau, E.; Frey, H.; Schlotterbeck, U.; Mecking, S.; Richtering, W. Hyperbranched Polymers: Structure of Hyperbranched Polyglycerol and Amphiphilic Poly(Glycerol Ester)s in Dilute Aqueous and Nonaqueous Solution. Macromolecules 2004, 37, 8394. (63) Satoh, T.; Imai, T.; Ishihara, H.; Maeda, T.; Kitajyo, Y.; Sakai, Y.; Kaga, H.; Kaneko, N.; Ishii, F.; Kakuchi, T. Synthesis, Branched Structure, and Solution Property of Hyperbranched D-Glucan and D-Galactan. Macromolecules 2005, 38, 4202. (64) Mulder, T.; Lyulin, A. V.; van der Schoot, P.; Michels, M. A. J. Architecture and Conformation of Uncharged and Charged Hyperbranched Polymers: Computer Simulation and Mean-Field Theory. Macromolecules 2005, 38, 996. (65) Elias, H. G.; Macromolecules, Volume 3: Physical Structures and Properties; Wiley-VCH: Weinheim, Germany, 2008. (66) Xu, M.; Yan, X. H.; Cheng, R. S.; Yu, X. H. Investigation into the Solution Properties of Hyperbranched Polymer. Polym. Int. 2001, 50, 1338. (67) Nunez, C. M.; Chiou, B. S.; Andrady, A. L.; Khan, S. A. Solution Rheology of Hyperbranched Polyesters and Their Blends With Linear Polymers. Macromolecules 2000, 33, 1720. (68) Ishizu, K.; Takahashi, D.; Takeda, H. Novel Synthesis and Characterization of Hyperbranched Polymers. Polymer 2000, 41, 6081. (69) Turner, S. R.; Voit, B. I.; Mourey, T. H. All-Aromatic Hyperbranched Polyesters with Phenol and Acetate End Groups: Synthesis and Characterization. Macromolecules 1993, 26, 4617. (70) Turner, S. R.; Walter, F.; Voit, B. I.; Mourey, T. H. Hyperbranched Aromatic Polyesters with Carboxylic Acid Terminal Groups. Macromolecules 1994, 27, 1611. (71) Kricheldorf, H. R.; Stoeber, O. New Polymer Syntheses, 76. Hyperbranched Polyesters by Polycondensation of Silylated 5-Acetoxyisophthalic Acid. Macromol. Rapid Commun. 1994, 15, 87. (72) Jiang, Y.; Frećhet, J. M. J. Synthesis of Branched Polymers Through Graft Copolymerization: Grafting of Isobutylene Onto Polystyrene by a Living Cationic Process. Polym. Prepr. (Am. Chem. Soc., DiV. Polym. Chem.) 1989, 30, 127. (73) Frećhet, J. M. J. Hawker, C. J. J. Philippides, A. E. Dendritic Molecules and Method of Production, U.S. Patent 5,041,516, August 20, 1991. (74) Hawker, C.; Frećhet, M. J. A New Convergent Approach to Monodisperse Dendritic Macromolecules. J. Chem. Soc., Chem. Commun. 1990, 1010. (75) Hawker, C. J.; Frećhet, J. M. J. Preparation of Polymers With Controlled Molecular Architecture. A New Convergent Approach to Dendritic Macromolecules. J. Am. Chem. Soc. 1990, 112, 7638. (76) Hawker, C. J.; Devonport, W. Design, Synthesis, and Properties of Dendritic Macromolecules. ACS Symp. Ser. 1996, 624, 186. (77) Hawker, C. J. Three-Dimensional Dendritic Macromolecules. Curr. Opin. Colloid Interface Sci. 1999, 4, 117. (78) Seiler, M.; Rolker, J.; Arlt, W. Phase Behavior and Thermodynamic Phenomena of Hyperbranched Polymer Solutions. Macromolecules 2003, 36, 2085. (79) James, D.; Bernquest, H.; Gustavsonn, E.; Ha¨ggman, B.; Danedll, P. Hyperbranched Polymers for Hardcoat with Superior Performance. Tuliao Gongye 2006, http://www.pcimag.com/Articles/Feature_Article/ 3f87df2575c49010VgnVCM100000f932a8c0, published online February 8, 2006. (80) Froehling, P. Development of DSM’s Hybrane Hyperbranched Polyesteramides. J. Polym. Sci., Part A: Polym. Chem. 2004, 42, 3110. (81) Bruchman, B.; Koniger, R.; Renz, H. Tailor-Made Crosslinkers for High Performance PUR Coatings-Hyperbranched Polyisocyanates. Macromol. Symp. 2002, 187, 271.

(82) Jikei, M.; Kakimoto, M. Hyperbranched Polymers: A Promising New Class of Materials. Prog. Polym. Sci. 2001, 26, 1233. (83) Seiler, M.; Kohler, D.; Arlt, W. Hyperbranched Polymers: New Selective Solvents for Extractive Distillation and Solvent Extraction. Sep. Purif. Technol. 2003, 30, 179. (84) Frey, H.; Haag, R. Dendritic Polyglycerol: A New Versatile Biocompatible Material. ReV. Mol. Biotechnol. 2002, 90, 257. (85) Yates, C. R.; Hayes, W. Synthesis and Applications of Hyperbranched Polymers. Eur. Polym. J. 2004, 40, 1257. (86) Gao, C.; Yan, D. Hyperbranched Polymers: From Synthesis to Applications. Prog. Polym. Sci. 2004, 29, 183. (87) Benita, S. Microencapsulation: Methods and Industrial Applications; Marcel Dekker: New York, 1996. (88) Ranade, V. V.; Hollinger, M. A. Drug DeliVery Systems; CRC Press: New York, 2003. (89) Mathiowitz, E.; Chickering, D. E.; Lehr, C. M. BioadhesiVe Drug DeliVery Systems: Fundamentals, NoVel Approaches, and DeVelopment; CRC Press: New York, 1999. (90) Häfeli, U. Radioactive Microspheres for Medical Applications. In Physics and Chemistry Basis of Biotechnology; De Cuyper, M., Bulte, J. W. M., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2001; pp 213-248. (91) Williams, R. O., III; Taft, D. R.; McConville, J. T. Advanced Drug Formulation Design to Optimize Therapeutic Outcomes. Drugs Pharm. Sci. 2008, 172, 510. (92) Bae, Y. H. Handbook of Pharmaceutical Controlled Release Technology; Wise, D. L., Ed.; CRC Press: New York, 2001; pp 553-554. (93) Hof, F.; Craig, S. L.; Nuckolls, C.; Rebek, J. Molecular Encapsulation. Angew. Chem., Int. Ed. 2002, 41, 1488. (94) Wan, D.; Yuan, J.; Pu, H. Macromolecular Nanocapsule Derived from Hyperbranched Polyethylenimine (HPEI): Mechanism of Guest Encapsulation versus Molecular Parameters. Macromolecules 2009, 42, 1533. (95) Rosen, M. R. DeliVery System Handbook for Personal Care and Cosmetic Products: Technology, Applications, and Formulations; William Andrew Publishing: New York, 2005. (96) Gibbs, B. F.; Kermasha, S.; Alli, I.; Mulligan, C. N. Encapsulation in the Food Industry: a Review. Int. J. Food Sci. Nutr. 1999, 50, 213. (97) Szejtli, J.; Szente, L.; Banky-Elod, E. Molecular Encapsulation of Volatile, Easily Oxidizable Labile Flavor Substances by Cyclodextrins. Acta Chim. Acad. Sci. Hung. 1979, 101, 27. (98) Masters, K. Impact of Spray Dryer Design on Powder Properties. In Drying ’91; Elsevier: Amsterdam, 1991; pp 56-73. (99) Green, B. K. Microscopic Capsules Containing Oil, U.S. Patent 2,800,458, July 23, 1957. (100) Arshady, R. Microspheres and Microcapsules, a Survey of Manufacturing Techniques. Part II: Coacervation. Polym. Eng. Sci. 1990, 30, 905. (101) Dingler, A.; Blum, R. P.; Niehus, H.; Muller, R. H.; Gohla, S. Solid Lipid Nanoparticles (SLN/Lipopearls)sA Pharmaceutical and Cosmetic Carrier for the Application of Vitamin E in Dermal Products. J. Microencapsulation 1999, 16, 751. (102) Scher, H. B.; Rodson, M.; Lee, K. S. Microencapsulation of Pesticides by Interfacial Polymerization Utilizing Isocyanate or Aminoplast Chemistry. Pestic. Sci. 1998, 54, 394. (103) Nelson, G. Application of Microencapsulation in Textiles. Int. J. Pharm. 2002, 242, 55. (104) Cho, J. S.; Kwon, A.; Cho, C. G. Microencapsulation of Octadecane as a Phase-Change Material by Interfacial Polymerization in an Emulsion System. Colloid Polym. Sci. 2002, 280, 260. (105) Re, M. I. Microencapsulation by Spray Drying. Dry. Technol. 1998, 16, 1195. (106) Dewettinck, K.; Huyghebaert, A. Fluidized Bed Coating in Food Technology. Trends Food Sci. Technol. 1999, 10, 163. (107) King, C.-K.; Tan, C.-T.; Scharpf, L. G., Jr.; O’Chat, D. P.; Schulman, M. Fluidizing Spray Chilling System for Producing Encapsulated Materials, U.S. Patent 5,417,153, May 23, 1995. (108) Bodmeier, R.; Wang, J.; Bhagwatwar, H. Process and Formulation Variables in the Preparation of Wax Microparticles by a Melt Dispersion Technique. II. W/O/W Multiple Emulsion Technique for Water-Soluble Drugs. J. Microencapsulation 1992, 9, 99. (109) Thies, C. A Survey of Microencapsulation Processes. In Microencapsulation: Methods and Industrial Applications; Marcel Dekker: New York, 1996. (110) Karasulu, E.; Karaca, B.; Alparslan, L.; Karasulu, H. Y. Places of Microemulsion and Emulsion in Cancer Therapy: In Vitro and In Vivo Evaluation. In Microemulsions: Properties and Applications; Fanun, M., Eds.; CRC Press: New York, 2008.

Ind. Eng. Chem. Res., Vol. 49, No. 3, 2010 (111) Lawrence, M. J.; Rees, G. D. Microemulsion-based media as novel drug delivery systems. AdV. Drug DeliVery ReV. 2000, 45, 89. (112) McDonald, C. J.; Bouck, K. J.; Chaput, A. B.; Stevens, C. J. Emulsion Polymerization of Voided Particles by Encapsulation of a Nonsolvent. Macromolecules 2000, 33, 1593. (113) Asua, J. M. Miniemulsion polymerization. Prog. Polym. Sci. 2002, 27, 1283. (114) Watts, P. J.; Davies, M. C.; Melia, C. D. Microencapsulation Using Emulsification/Solvent Evaporation: an Overview of Techniques and Applications. Crit. ReV. Ther. Drug Carrier Syst. 1990, 7, 235. (115) Beckman, E. J. Supercritical and Near-Critical CO2 in Green Chemical Synthesis and Processing. J. Supercrit. Fluids 2004, 28, 121. (116) Weidner, E.; Steiner, R.; Knez, Z. Powder Generation from Polyethylene Glycols with Compressible Fluids. Process Technol. Proc. 1996, 12, 223. (117) Smith, R. D. Supercritical Fluid Molecular Spray Film Deposition and Powder Formation, U.S. Patent 4,582,731, April 15, 1986. (118) Jung, J.; Perrut, M. Particle Design Using Supercritical Fluids: Literature and Patent Survey. J. Supercrit. Fluids. 2001, 20, 179. (119) Schmitt, W. J. Preparation of Finely Divided Solid Crystalline Powders Via Precipitation into an Antisolvent, World Patent WO 9003782, 1989. (120) Fages, J.; Lochard, H.; Letourneau, J. J.; Sauceau, M.; Rodier, E. Particle Generation for Pharmaceutical Applications Using Supercritical Fluid Technology. Powder Technol. 2004, 141, 219. (121) Bungert, B.; Sadowski, G.; Arlt, W. Separations and Material Processing in Solutions with Dense Gases. Ind. Eng. Chem. Res. 1998, 37, 3208. (122) Reverchon, E. Supercritical Antisolvent Precipitation of Microand Nano-Particles. J. Supercrit. Fluids 1999, 15, 1. ´ .; Matteaa, F.; Varonaa, S. Encapsulation (123) Cocero, M. J.; Martıńa, A and co-precipitation processes with supercritical fluids: Fundamentals and applications. J. Supercrit. Fluids 2009, 47, 546. (124) Duncan, R. The Dawning Era of Polymer Therapeutics. Nat. ReV. Drug DiscoVery 2003, 2, 347. (125) Pasut, G.; Veronese, F. M. Polymer-Drug Conjugation, Recent Achievements and General Strategies. Prog. Polym. Sci. 2007, 32, 933. (126) Palmer, L. C.; Rebek, J., Jr. The Ins and Outs of Molecular Encapsulation. Org. Biomol. Chem. 2004, 2, 3051. (127) Reinhoudt, D. N.; Crego-Calama, M. Synthesis Beyond the Molecule. Science (Washington, DC, U.S.A.) 2002, 295, 2403. (128) Newkome, G. R. Unimolecular Micelles. NATO ASI Ser. Ser. C 1992, 371, 145. (129) Schmaljohann, D.; Poetschke, P.; Haessler, R.; Voit, B. I.; Froehling, P. E.; Mostert, B.; Loontjens, J. A. Blends of Amphiphilic, Hyperbranched Polyesters and Different Polyolefins. Macromolecules 1999, 32, 6333. (130) Gooden, J. K.; Gross, M. L.; Mu¨ller, A.; Stefanescu, A. D.; Wooley, K. L. Cyclization in Hyperbranched Polymer Syntheses: Characterization by MALDI-TOF Mass Spectrometry. J. Am. Chem. Soc. 1998, 120, 10180. (131) Kostanski, L. K.; Keller, D. M.; Hamielec, A. E. Size-Exclusion ChromatographysA Review of Calibration Methodologies. J. Am. Chem. Soc. 2004, 58, 159. (132) Peacock, P. M.; McEwen, C. N. Mass spectrometry of synthetic polymers. Anal. Chem. 2004, 76, 3417. (133) Burgath, A.; Sunder, A.; Frey, H. Role of Cyclization in the Synthesis of Hyperbranched Aliphatic Polyesters. Macromol. Chem. Phys. 2000, 201, 782. (134) Uhrich, K. E. Hyperbranched Polymers for Drug Delivery. Trends Polym. Sci. 1997, 5, 388. (135) Kreutzer, G.; Ternat, C.; Nguyen, T. Q.; Plummer, C. J. G.; Manson, J. A. E.; Castelletto, V.; Hamley, I. W.; Sun, F.; Sheiko, S. S.; Herrmann, A. Water-Soluble, Unimolecular Containers Based on Amphiphilic Multiarm Star Block Copolymers. Macromolecules 2006, 39, 4507. (136) Mecking, S.; Thomann, R.; Frey, H.; Sunder, A. Preparation of Catalytically Active Palladium Nanoclusters in Compartments of Amphiphilic Hyperbranched Polyglycerols. Macromolecules 2000, 33, 3958. (137) Adeli, M.; Haag, R. Multiarm Star Nanocarriers Containing a Poly(Ethylene Imine) Core and Polylactide Arms. J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 5740. (138) Arkas, M.; Eleades, L.; Paleos, C. M.; Tsiourvas, D. Alkylated Hyperbranched Polymers as Molecular Nanosponges for the Purification of Water from Polycyclic Aromatic Hydrocarbons. J. Appl. Polym. Sci. 2005, 97, 2299. (139) Yeo, S. D.; Kiran, E. Formation of Polymer Particles with Supercritical Fluids: A Review. J. Supercrit. Fluids 2005, 34, 287. (140) Tom, J. W.; Debenedetti, P. G. Particle Formation with Supercritical FluidssA Review. J. Aerosol Sci. 1991, 22, 555.

1193

(141) Debenedetti, P. G.; Tom, J. W.; Yeo, S.; Lim, G. B. Application of Supercritical Fluids for the Production of Sustained Delivery Devices. J. Controlled Release 1993, 24, 27. (142) Subramaniam, B.; Rajewski, R. A.; Snavely, K. Pharmaceutical Processing with Supercritical Carbon Dioxide. J. Pharm. Sci. 1997, 86, 885. (143) Roy, J. Pharmaceutical ImpuritiessA Mini-Review. AAPS PharmSciTech 2002, 3, Article No. 6. (144) Lee, C. C.; Mackay, J. A.; Frećhet, J. M. J.; Szoka, F. C. Designing Dendrimers for Biological Applications. Nat. Biotechnol. 2005, 23, 1517. (145) Varga, T. K. DeVelopment and Application of Nitrite-Free and Low-Nitrite Meat-Curing Systems, Ph.D. Dissertation, University of Toronto, Canada, 1997. (146) Chen, Y.; Frey, H.; Thomann, R.; Stiriba, S. E. Optically Active Amphiphilic Hyperbranched Polyglycerols As Templates for Palladium Nanoparticles. Inorg. Chim. Acta 2006, 359, 1837. (147) Hirano, T.; Ihara, H.; Miyagi, T.; Wang, H.; Seno, M.; Sato, T. Formation of Soluble Hyperbranched Polymer Nanoparticles by InitiatorFragment Incorporation Radical Polymerization of Ethylene Glycol Dimethacrylate. Macromol. Chem. Phys. 2005, 206, 860. (148) Kitajyo, Y.; Nawa, Y.; Tamaki, M.; Tani, H.; Takahashi, K.; Kaga, H.; Satoh, T.; Kakuchi, T. A Unimolecular Nanocapsule: Encapsulation Property of Amphiphilic Polymer Based on Hyperbranched Polythreitol. Polymer 2007, 48, 4683. (149) Liu, H. J.; Chen, Y.; Zhu, D. D.; Shen, Z.; Stiriba, S. E. Hyperbranched Polyethylenimines as Versatile Precursors for the Preparation of Different Type of Unimolecular Micelles. React. Funct. Polym. 2007, 67, 383. (150) Zou, J. H.; Shi, W. F.; Wang, J.; Jun, B. Encapsulation and Controlled Release of a Hydrophobic Drug Using a Novel NanoparticleForming Hyperbranched Polyester. Macromol. Biosci. 2005, 5, 662. (151) Hawlader, M. N. A.; Uddin, M. S.; Khin, M. M. Microencapsulated PCM Thermal-Energy Storage System. Appl. Energy 2003, 74, 195. (152) Mathiowitz, E.; Langer, R. Polyanhydride Microspheres as Drug Carriers. I. Hot-Melt Microencapsulation. J. Controlled Release 1987, 5, 13. (153) Suttiruengwong, S.; Rolker, J.; Smirnova, I.; Arlt, W.; Seiler, M.; Luderitz, L.; de Diego, Y. P.; Jansens, P. J. Hyperbranched Polymers as Drug Carriers: Microencapsulation and Release Kinetics. Pharm. DeV. Technol. 2006, 11, 55. (154) Schappacher, M.; Deffieux, A. Encapsulation of Metallo-Porphyrins into Water-Soluble Amphipatic Dendrigrafts. Polymer 2004, 45, 4633. (155) Tian, H. Y.; Chen, X. S.; Lin, H.; Deng, C.; Zhang, P. B.; Wei, Y.; Jing, X. B. Micellization and Reversible PH-Sensitive Phase Transfer of the Hyperbranched Multiarm PEI-PBLG Copolymer. Chem.sEur. J. 2006, 12, 4305. (156) Seiler, M.; Klee, S.; Hills, G.; Lersch, P.; Smirnova, I.; Arlt, W.; Tschernjaew, J.; Kobus, A. Biologically Active Substances for Controlled Release Encapsulated in Enzymatically Degradable Hyperbranched Carrier Polymers, World Patent WO 2007048464, 2007. (157) Chen, Y.; Shen, Z.; Pastor-Perez, L.; Frey, H.; Stiriba, S. E. Role of Topology and Amphiphilicity for Guest Encapsulation in Functionalized Hyperbranched Poly(ethylenimine)s. Macromolecules 2005, 38, 227. (158) Slagt, M. Q.; Stiriba, S. E.; Kautz, H.; Gebbink, R. J. M. K.; Frey, H.; van Koten, G. Optically Active Hyperbranched Polyglycerol As Scaffold for Covalent and Noncovalent Immobilization of Platinum(II) NCN-Pincer Complexes. Catalytic Application and Recovery. Organometallics 2004, 23, 1525. (159) Wan, D. C.; Fu, Q.; Huang, J. L. Synthesis of Amphiphilic Hyperbranched Polyglycerol Polymers and Their Application as Template for Size Control of Gold Nanoparticles. J. Appl. Polym. Sci. 2006, 101, 509. (160) Seiler, M.; Windhab, N.; Stickler, M.; Petereit, H.-U. Drug Delivery Systems Containing Dendritic Polymers and Signal Peptides, World Patent WO 2007048599, 2007. (161) Liu, H. J.; Zhong, S.; Striba, S. E.; Chen, Y.; Zhang, W. Q.; Wei, L. H. Core-Shell-Type Multiarm Star Polyethylenirnine-Block-Poly(EpsilonCaprolactone): Synthesis and Guest Encapsulation Potential. J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 4165. (162) Slagt, M. Q.; Stiriba, S. E.; Gebbink, R. J. M. K.; Kautz, H.; Frey, H.; van Koten, G. Encapsulation Off Hydrophilic Pincer-Platinum(II) Complexes in Amphiphilic Hyperbranched Polyglycerol Nanocapsules. Macromolecules 2002, 35, 5734. (163) Tziveleka, L. A.; Kontoyianni, C.; Sideratou, Z.; Tsiourvas, D.; Paleos, C. M. Novel Functional Hyperbranched Polyether Polyols as Prospective Drug Delivery Systems. Macromol. Biosci. 2006, 6, 161. (164) Huang, X.; Brazel, C. S. On the Importance and Mechanisms of Burst Release in Matrix-Controlled Drug Delivery Systems. J. Controlled Release 2001, 73, 121.

1194


(165) Pettersson, B. Hyperbranched Polymers: Unique Design Tools for Multi-Property Control in Resins and Coatings. Pigment Resin Technol. 1996, 25, 4. (166) Seiler, M.; Kobus, A. Formulations Containing Hyperbranched Polymers, World Patent WO 2007048672, 2007. (167) Adeli, M.; Haag, R.; Zarnegar, Z. Effect of the Shell on the Transport Properties of Poly(glycerol) and Poly(ethylene imine) Nanoparticles. J. Nanopart. Res. 2007, 9, 1057. (168) Koerner, A.; Larsson, A.; Piculell, L.; Wittgren, B. Molecular Information on the Dissolution of Polydisperse Polymers: Mixtures of Long and Short Poly(Ethylene Oxide). J. Phys. Chem. B 2005, 109, 11530. (169) Berchane, N. S.; Carson, K. H.; Rice-Ficht, A. C.; Andrews, M. J. Effect of Mean Diameter and Polydispersity of PLG Microspheres on Drug Release: Experiment and Theory. Int. J. Pharm. 2007, 337, 118. (170) Wang, X. L.; Jensen, R.; Lu, Z. R. A Novel Environment-Sensitive Biodegradable Polydisulfide with Protonatable Pendants for Nucleic Acid Delivery. J. Controlled Release 2007, 120, 250. (171) Wooley, K. L.; Hawker, C. J.; Lee, R.; Frećhet, J. M. J. OneStep Synthesis of Hyperbranched Polyesters. Molecular Weight Control and Chain End Functionalization. Polym. J. (Tokyo) 1994, 26, 187. (172) Prabaharan, M.; Grailer, J. J.; Pilla, S.; Steeber, D. A.; Gong, S. Folate-Conjugated Amphiphilic Hyperbranched Block Copolymers Based on Boltorn H40, Poly(L-lactide) and Poly(ethylene glycol) for TumorTargeted Drug Delivery. Biomaterials 2009, 30, 3009. (173) Satoh, T.; Tamaki, M.; Kitajyo, Y.; Maeda, T.; Ishihara, H.; Imai, T.; Kaga, H.; Kakuchi, T. Synthesis of Unimolecular Reversed Micelle Consisting of a Poly(L-Lactide) Shell and Hyperbranched D-Mannan Core. J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 406. (174) Xu, S.; Luo, Y.; Haag, R. Water-Soluble pH-Responsive Dendritic Core-Shell Nanocarriers for Polar Dyes Based on Poly(ethylene imine). Macromol. Biosci. 2007, 7, 968. (175) Xu, S. J.; Kra¨mer, M.; Haag, R. PH-Responsive Dendritic CoreShell Architectures as Amphiphilic Nanocarriers for Polar Drugs. J. Drug Targeting 2006, 14, 367. (176) Voit, B. I. Dendritic Polymers: From Aesthetic Macromolecules to Commercially Interesting Materials. Acta Polym. 1995, 46, 87. (177) Leach, W. T.; Simpson, D. T.; Val, T. N.; Yu, Z.; Lim, K. T.; Park, E. J.; Williams, R. O., III.; Johnston, K. P. Encapsulation of Protein Nanoparticles into Uniform-Sized Microspheres Formed in a Spinning Oil Film. AAPS PharmSciTech 2005, 6, E605. (178) Liu, H. J.; Chen, Y.; Shen, Z.; Frey, H. Multiarm Star PolyglycerolBlock-Poly(HEMA) as a Versatile Precursor for the Preparation of Micellar Nanocapsules with Different Properties. React. Funct. Polym. 2007, 67, 156. (179) Gottschalk, C.; Wolf, F.; Frey, H. Multi-Arm Star Poly(L-Lactide) with Hyperbranched Polyglycerol Core. Macromol. Chem. Phys. 2007, 208, 1657. (180) Sato, T.; Nobutane, H.; Hirano, T.; Seno, M. Hyperbranched Acrylate Copolymer Via Initiator-Fragment Incorporation Radical Copolymerization of Divinylbenzene and Ethyl Acrylate: Synthesis, Characterization, Hydrolysis, Dye-Solubilization, Ag Particle-Stabilization, and Porous Film Formation. Macromol. Mater. Eng. 2006, 291, 162. (181) Kitajyo, Y.; Imai, T.; Sakai, Y.; Tamaki, M.; Tani, H.; Takahashi, K.; Narumi, A.; Kaga, H.; Kaneko, N.; Satoh, T. Encapsulation-Release Property of Amphiphilic Hyperbranched D-Glucan As a Unimolecular Reverse Micelle. Polymer 2007, 48, 1237. (182) Khandare, J.; Minko, T. Polymer-Drug Conjugates: Progress in Polymeric Prodrugs. Prog. Polym. Sci. 2006, 31, 359. (183) Sideratou, Z.; Tziveleka, L. A.; Kontoyianni, C.; Tsiourvas, D.; Paleos, C. M. Design of Functional Dendritic Polymers for Application as Drug and Gene Delivery Systems. Gene Ther. Mol. Biol. 2006, 10A, 71. (184) Paleos, C. M.; Tsiourvas, D.; Sideratou, Z. Molecular Engineering of Dendritic Polymers and Their Application as Drug and Gene Delivery Systems. Mol. Pharmaceutics 2007, 4, 169. (185) Kra¨mer, M.; Kopaczynska, M.; Krause, S.; Haag, R. Dendritic Polyamine Architectures with Lipophilic Shells as Nanocompartments for Polar Guest Molecules: A Comparative Study of Their Transport Behavior. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 2287. (186) Kainthan, R. K.; Hester, S. R.; Levin, E.; Devine, D. V.; Brooks, D. E. In Vitro Biological Evaluation of High Molecular Weight Hyperbranched Polyglycerols. Biomaterials 2007, 28, 4581. (187) Kainthan, R. K.; Brooks, D. E. In Vivo Biological Evaluation of High Molecular Weight Hyperbranched Polyglycerols. Biomaterials 2007, 28, 4779. (188) Mallepally, R. R. Encapsulation and Controlled Release of Pharmaceuticals with Biodegradable Hyperbranched Polyesters, Ph.D. Dissertation, University of Erlangen-Nuremberg, Germany, 2009. (189) Tang, L. M.; Fang, Y.; Tang, X. L. Influence of Alkyl Chains of Amphiphilic Hyperbranched Poly(Ester Amine)s on the Phase-Transfer

Performances for Acid Dye and the Aggregation Behaviors at the Interface. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 2921. (190) Sutton, D.; Durand, R.; Shuai, X. T.; Gao, J. M. Poly(D,L-LactideCo-Glycolide)/Poly(Ethylenimine) Blend Matrix System for pH Sensitive Drug Delivery. J. Appl. Polym. Sci. 2006, 100, 89. (191) Hu, H.; Fan, X. D.; Cao, Z. L.; Cheng, W. X.; Liu, Y. Y. Synthesis and Characterization of the Environmental-Sensitive Hyperbranched Polymers as Novel Carriers for Controlled Drug Release. J. Appl. Polym. Sci. 2006, 101, 311. (192) Kolhe, P.; Khandare, J.; Pillai, O.; Kannan, S.; Lieh-Lai, M.; Kannan, R. Hyperbranched Polymer-Drug Conjugates with High Drug Payload for Enhanced Cellular Delivery. Pharm. Res. 2004, 21, 2185. (193) Pal, K.; Banthia, A. K.; Majumdar, D. K. Polymeric Hydrogels: Characterization and Biomedical Applications. Des. Monomers Polym. 2009, 12, 197. (194) Olefsky, J. M. Diabetes: Gene Therapy for Rats and Mice. Nature (London) 2000, 408, 420. (195) Gao, X.; Kim, K.; Liu, D. Nonviral Gene Delivery: What We Know and What Is Next. AAPS J. 2007, 9, E92. (196) Niidome, T.; Huang, L. Gene Therapy Progress and Prospects: Nonviral Vectors. Gene Ther. 2002, 9, 1647. (197) Boussif, O.; Lezoualch, F.; Zanta, M. A.; Mergny, M. D.; Scherman, D.; Demeneix, B.; Behr, J. P. A Versatile Vector for Gene and Oligonucleotide Transfer Into Cells in Culture and In-Vivo-Polyethylenimine. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 7297. (198) Godbey, W. T.; Wu, K. K.; Mikos, A. G. Poly(Ethylenimine)Mediated Gene Delivery Affects Endothelial Cell Function and Viability. Biomaterials 2001, 22, 471. (199) Petersen, H.; Fechner, P. M.; Martin, A. L.; Kunath, K.; Stolnik, S.; Roberts, C. J.; Fischer, D.; Davies, M. C.; Kissel, T. PolyethylenimineGraft-Poly(Ethylene Glycol) Copolymers: Influence of Copolymer Block Structure on DNA Complexation and Biological Activities as Gene Delivery System. Bioconjugate Chem. 2002, 13, 845. (200) Wang, C. H.; Hsiue, G. H. Polymer-DNA Hybrid Nanoparticles Based on Folate-Polyethylenimine-Block-Poly(L-Lactide). Bioconjugate Chem. 2005, 16, 391. (201) Lin, C.; Zhong, Z.; Lok, M. C.; Jiang, X.; Hennink, W. E.; Feijen, J.; Engbersen, J. F. J. Novel Bioreducible Poly(Amido Amine)s for Highly Efficient Gene Delivery. Bioconjugate Chem. 2007, 18, 138. (202) Ahn, C. H.; Chae, S. Y.; Bae, Y. H.; Kim, S. W. Biodegradable Poly(ethylenimine) for Plasmid DNA Delivery. J. Controlled Release 2002, 80, 273. (203) Pack, D. W.; Hoffman, A. S.; Pun, S.; Stayton, P. S. Design and Development of Polymers for Gene Delivery. Nat. ReV. Drug DiscoVery 2005, 4, 581. (204) Tian, H. Y.; Xiong, W.; Wei, J. Z.; Wang, Y.; Chen, X. S.; Jing, X. B.; Zhu, Q. Y. Gene Transfection of Hyperbranched PEI Grafted by Hydrophobic Amino Acid Segment PBLG. Biomaterials 2007, 28, 2899. (205) Tian, H. Y.; Deng, C.; Lin, H.; Sun, J. R.; Deng, M. X.; Chen, X. S.; Jing, X. B. Biodegradable Cationic PEG-PEI-PBLG Hyperbranched Block Copolymer: Synthesis and Micelle Characterization. Biomaterials 2005, 26, 4209. (206) Kim, T. H.; Cook, S. E.; Arote, R. B.; Cho, M. H.; Nah, J. W.; Choi, Y. J.; Cho, C. S. A Degradable Hyperbranched Poly(ester amine) Based on Poloxamer Diacrylate and Polyethylenimine as a Gene Carrier. Macromol. Biosci. 2007, 7, 611. (207) Kim, T. I.; Seo, H. J.; Choi, J. S.; Yoon, J. K.; Baek, J. U.; Kim, K.; Park, J. S. Synthesis of Biodegradable Cross-Linked Poly(Beta-Amino Ester) for Gene Delivery and Its Modification, Inducing Enhanced Transfection Efficiency and Stepwise Degradation. Bioconjugate Chem. 2005, 16, 1140. (208) Wu, D. C.; Liu, Y.; Jiang, X.; He, C. B.; Goh, S. H.; Leong, K. W. Hyperbranched Poly(Amino Ester)s With Different Terminal Amine Groups for DNA Delivery. Biomacromolecules 2006, 7, 1879. (209) Lim, Y.; Choi, Y. H.; Park, J. A Self-destroying Polycationic Polymer: Biodegradable Poly (4-hydroxy-L-proline ester). Macromolecules 1992, 25, 4476. (210) Kim, H. J.; Kwon, M. S.; Choi, J. S.; Yang, S. M.; Yoon, J. K.; Kim, K.; Park, J. S. Highly Effective and Slow-Biodegradable NetworkType Cationic Gene Delivery Polymer: Small Library-Like Approach Synthesis and Characterization. Biomaterials 2006, 27, 2292. (211) Rihova, B.; Riha, I. Immunological Problems of Polymer-Bound Drugs. Crit. ReV. Ther. Drug Carrier Syst. 1985, 1, 311. (212) Rihova, B. Biocompatibility of Biomaterials: Hemocompatibility, Immunocompatibility and Biocompatibility of Solid Polymeric Materials and Soluble Targetable Polymeric Carriers. AdV. Drug DeliVery ReV. 1996, 21, 157.

Ind. Eng. Chem. Res., Vol. 49, No. 3, 2010 (213) Petersen, H.; Fechner, P. M.; Fischer, D.; Kissel, T. Synthesis, Characterization, and Biocompatibility of Polyethylenimine-GraftPoly(ethylene glycol) Block Copolymers. Macromolecules 2002, 35, 6867. (214) Godbey, W. T.; Wu, K. K.; Mikos, A. G. Size Matters: Molecular Weight Affects the Efficiency of Poly(ethylenimine) as a Gene Delivery Vehicle. J. Biomed. Mater. Res. 1999, 45, 268. (215) Fischer, D.; Bieber, T.; Li, Y.; Elsasser, H. P.; Kissel, T. A Novel Non-Viral Vector for DNA Delivery Based on Low Molecular Weight, Branched Polyethylenimine: Effect of Molecular Weight on Transfection Efficiency and Cytotoxicity. Pharm. Res. 1999, 16, 1273. (216) Kainthan, R. K.; Janzen, J.; Levin, E.; Devine, D. V.; Brooks, D. E. Biocompatibility Testing of Branched and Linear Polyglycidol. Biomacromolecules 2006, 7, 703. (217) Mu¨ller, R. H., Hildebrand, G. E., Eds. Pharmazeutische Technologie: Moderne Arzneiformen; Wissenschaftliche Verlagsgesellschaft: Stuttgart, Germany, 1998. (218) Wischke, C.; Schwendeman, S. P. Principles of Encapsulating Hydrophobic Drugs in PLA/PLGA Microparticles. Int. J. Pharm. 2008, 364, 298. (219) Dittgen, M.; Durrani, M.; Lehmann, K. Acrylic Polymers: A Review of Pharmaceutical Applications. STP Pharma Sci. 1997, 7, 403. (220) Fahr, A.; Kissel, T. Mikropartikel Und Implantate: Arzneiformen Zur Parenteralen Applikation. In Pharmazeutische Technologie: Moderne Arzneiformen; Mu¨ller, R. H., Hildebrand, G. E., Eds.; Wissenschaftliche Verlagsgesellschaft: Stuttgart, Germany, 1998. (221) Mu¨ller, R. H.; Mader, K.; Gohla, S. Solid Lipid Nanoparticles (SLN) for Controlled Drug DeliverysA Review of the State of the Art. Eur. J. Pharm. Biopharm. 2000, 50, 161. (222) Mu¨ller, R. H.; Maassen, S.; Weyhers, H.; Specht, F.; Lucks, J. S. Cytotoxicity of Magnetite-Loaded Polylactide, Polylactide/Glycolide Particles and Solid Lipid Nanoparticles. Int. J. Pharm. 1996, 138, 85. (223) Pillai, O.; Panchagnula, R. Polymers in Drug Delivery. Curr. Opin. Chem. Biol. 2001, 5, 447. (224) Roberts, J. C.; Bhalgat, M. K.; Zera, R. T. Preliminary Biological Evaluation of Polyamidoamine (PAMAM) Starburst Dendrimers. J. Biomed. Mater. Res. 1996, 30, 53. (225) Bourne, N.; Stanberry, L. R.; Kern, E. R.; Holan, G.; Matthews, B.; Bernstein, D. I. Dendrimers, a New Class of Candidate Topical Microbiocides with Activity against Herpes Simplex Virus Infection. Antimicrob. Agents Chemother. 2000, 44, 2471. (226) Boas, U.; Heegaard, P. M. H. Dendrimers in Drug Research. Chem. Soc. ReV. 2004, 33, 43. (227) Seiler, M. Dendritic PolymerssInterdisciplinary Research and Emerging Applications from Unique Structural Properties. Chem. Eng. Technol. 2002, 25, 237. (228) Emrick, T. S. Amphiphilic Polymer Capsules and Interfacial Assembly of Capsules, World Patent WO 2005025736, 2005. (229) Kolhe, P.; Misra, E.; Kannan, R. M.; Kannan, S.; Lieh-Lai, M. Drug Complexation, in Vitro Release and Cellular Entry of Dendrimers and Hyperbranched Polymers. Int. J. Pharm. 2003, 259, 143. (230) Davidson, R. S.; Kehoe, G. Oral Composition Comprising Film Layer and Powder Matrix, World Patent WO 2007102817, 2007. (231) Malinin, V. Methods for Coacervation Induced Liposomal Encapsulation and Formulations Thereof, World Patent WO 2007117550, 2007. (232) Hughes, P. M. Retinoid-Containing Sustained Release Intraocular Drug Delivery Systems, World Patent WO 2005107707, 2005. (233) Bitz, C.; Doelker, E. Influence of the Preparation Method on Residual Solvents in Biodegradable Microspheres. Int. J. Pharm. 1996, 131, 171. (234) Dwivedi, A. M. Residual Solvent Analysis in Pharmaceuticals. Pharm. Technol. North Am. 2002, 26, 42, 44, 46. (235) Seiler, M.; Irfan, M. Method for Producing Microparticles From Hydrophobized Hyperbranched Polymer, World Patent WO 2008025640, 2008. (236) Bruza, K. J. Preparation of Hyperbranched Polymers Having Covalently Bound Fragrance Moieties for Sustained Fragrance Release, U.S. Patent Application 2006018977, 2006. (237) Ouali, L.; Herrmann, A.; Ternat, C.; Plummer, C. J. G.; Klok, H.-A.; Kreutzer, G.; Manson, J.-A. Amphiphilic Star-Shaped Block Copolymers and Its Preparation and Applications, World Patent WO 2006038110, 2006. (238) Fieber, W.; Herrmann, A.; Ouali, L.; Velazco, M. I.; Kreutzer, G.; Klok, H. A.; Ternat, C.; Plummer, C. J. G.; Manson, J. A. E.; Sommer, H. NMR Diffusion and Relaxation Studies of the Encapsulation of Fragrances by Amphiphilic Multiarm Star Block Copolymers. Macromolecules 2007, 40, 5372. (239) Ternat, C.; Kreutzer, G.; Plummer, C. J. G.; Nguyen, T. O.; Herrmann, A.; Ouali, L.; Sommer, H.; Fieber, W.; Velazco, M. I.; Klok,

1195

H. A. Amphiphilic Multi-Arm Star-Block Copolymers for Encapsulation of Fragrance Molecules. Macromol. Chem. Phys. 2007, 208, 131. (240) Uhrich, K. E. Hyperbranched Polymeric Micelles for Encapsulation and Delivery of Hydrophobic Drugs, World Patent WO 2000065024, 2000. (241) Seiler, M.; Haneke, M.; Marckmann, H.; Pilz, S.; Irfan, M.; Klee, S.; Hills, G.; Farwick, M.; Lersch, P.; Kobus, A. Preparation for the Controlled Release of Bioactive Natural Substances, World Patent WO 2008128924, 2008. (242) Bradley, J. S. The Chemistry of Transition Metal Colloids. Clusters Colloids 1994, 459. (243) Hajji, C.; Haag, R. Hyperbranched Polymers as Platforms for Catalysts. In Dendrimer Catalysis; Gade, L. H., Eds.; Springer: Berlin, 2006; pp 149-176. (244) Clark, J. H. Catalysis of Organic Reactions by Supported Inorganic Reagents; VCH Publishers: New York, 1994. (245) Crooks, R. M.; Zhao, M.; Sun, L.; Chechik, V.; Yeung, L. K. Dendrimer-Encapsulated Metal Nanoparticles: Synthesis, Characterization, and Applications to Catalysis. Acc. Chem. Res. 2001, 34, 181. (246) Pileni, M. P. Nanosized Particles Made in Colloidal Assemblies. Langmuir 1997, 13, 3266. (247) Chechik, V.; Zhao, M.; Crooks, R. M. Self-Assembled Inverted Micelles Prepared From a Dendrimer Template: Phase Transfer of Encapsulated Guests. J. Am. Chem. Soc. 1999, 121, 4910. (248) Chechik, V.; Crooks, R. M. Dendrimer-Encapsulated Pd Nanoparticles as Fluorous Phase-Soluble Catalysts. J. Am. Chem. Soc. 2000, 122, 1243. (249) Vriezema, D. M.; Aragones, M. C.; Elemans, J. A. A. W.; Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M. Self-Assembled Nanoreactors. Chem. ReV. 2005, 105, 1445. (250) Schlotterbeck, U.; Aymonier, C.; Thomann, R.; Hofmeister, H.; Tromp, M.; Richtering, W.; Mecking, S. Shape-Selective Synthesis of Palladium Nanoparticles Stabilized by Highly Branched Amphiphilic Polymers. AdV. Funct. Mater. 2004, 14, 999. (251) Sablong, R.; Schlotterbeck, U.; Vogt, D.; Mecking, S. Catalysis With Soluble Hybrids of Highly Branched Macromolecules With Palladium Nanoparticles in a Continuously Operated Membrane Reactor. AdV. Synth. Catal. 2003, 345, 333. (252) Stiriba, S. E.; Slagt, M. Q.; Kautz, H.; Gebbink, R. J. M. K.; Thomann, R.; Frey, H.; van Koten, G. Synthesis and Supramolecular Association of Immobilized NCN-Pincer Platinum(II) Complexes on Hyperbranched Polyglycerol Supports. Chem.sEur. J. 2004, 10, 1267. (253) Tabuani, D.; Monticelli, O.; Komber, H.; Russo, S. Preparation and Characterisation of Pd Nanoclusters in Hyperbranched Aramid Templates to be Used in Homogeneous Catalysis. Macromol. Chem. Phys. 2003, 204, 1576. (254) Zhu, Z. D.; Kai, L.; Wang, Y. C. Synthesis and Applications of Hyperbranched PolyesterssPreparation and Characterization of Crystalline Silver Nanoparticles. Mater. Chem. Phys. 2006, 96, 447. (255) Bochkarev, M. N.; Brezhneva, I. I.; Katkova, M. A.; Semchikov, Y. D.; Maksimov, G. A.; Gushchina, Y. Y.; Vitukhnovskii, A. G.; Lepnev, L. S. Intramolecular Impregnation of Hyperbranched Perfluorinated Poly(Phenylenepolygermane) In Situ by Lanthanide Fluorides. J. Polym. Sci., Part A: Polym. Chem. 2002, 44, 89. (256) Manziek, L.; Langenmayr, E.; Lamola, A.; Gallagher, M.; Brese, N.; Annan, N. Functionalized Emulsion and Suspension Polymer Particles: Nanoreactors for the Synthesis of Inorganic Materials. Chem. Mater. 1998, 10, 3101. (257) Zhao, M.; Sun, L.; Crooks, R. M. Preparation of Cu Nanoclusters within Dendrimer Templates. J. Am. Chem. Soc. 1998, 120, 4877. (258) Balogh, L.; Tomalia, D. A. Poly(amidoamine) Dendrimer-Templated Nanocomposites. 1. Synthesis of Zerovalent Copper Nanoclusters. J. Am. Chem. Soc. 1998, 120, 7355. (259) Esumi, K.; Suzuki, A.; Aihara, N.; Usui, K.; Torigoe, K. Preparation of Gold Colloids with UV Irradiation Using Dendrimers as Stabilizer. Langmuir 1998, 14, 3157. (260) Ng Cheong Chan, Y.; Schrock, R. R.; Cohen, R. E. Synthesis of Single Silver Nanoclusters Within Spherical Microdomains in Block Copolymer Films. J. Am. Chem. Soc. 1992, 114, 7295. (261) Saito, R.; Okamura, S.; Ishizu, K. Introduction of Colloidal Silver into a Poly(2-vinylpyridine) Microdomain of Microphase Separated Poly(styrene-b-2-vinylpyridine) Film. Polymer 1992, 33, 1099. (262) Antonietti, M.; Wenz, E.; Bronstein, L.; Seregina, M. Synthesis and Characterization of Noble Metal Colloids in Block Copolymer Micelles. AdV. Mater. (Weinheim, Ger.) 1995, 7, 1000. (263) Paleos, C. M.; Tsiourvas, D.; Sideratou, O.; Arkas, M. Manufacture of Modified Lipophilic Dendritic and Hyperbranched Polymers for Water Purification, World Patent WO 2004065459, 2004. (264) Arkas, M.; Allabashi, R.; Tsiourvas, D.; Mattausch, E. M.; Perfler, R. Organic/Inorganic Hybrid Filters Based on Dendritic and Cyclodextrin

1196


“Nanosponges” for the Removal of Organic Pollutants From Water. EnViron. Sci. Technol. 2006, 40, 2771. (265) Allabashi, R.; Arkas, M.; Hoermann, G.; Tsiourvas, D. Removal of Some Organic Pollutants in Water Employing Ceramic Membranes Impregnated With Cross-Linked Silylated Dendritic and Cyclodextrin Polymers. Water Res. 2007, 41, 476. (266) Tsetsekou, A.; Arkas, M.; Kritikaki, A.; Simonetis, S.; Tsiourvas, D. Optimization of Hybrid Hyperbranched Polymer/Ceramic Filters for the Efficient Absorption of Polyaromatic Hydrocarbons from Water. J. Membr. Sci. 2008, 311, 128. (267) Rousseau, R. W. Handbook of Separation Process Technology; John Wiley & Sons: New York, 1987. (268) Membrane Separations Technology: Principles and Application; Noble, R. D., Stern, S. A., Eds.; Elsevier Science: Amsterdam, 1995. (269) Chemical Separations with Liquid Membranes; Bartsch, R. A., Way, J. D., Eds.; American Chemical Society: Washington, DC, 1996. (270) Martin, T. P.; Davies, G. A. The Extraction of Copper from Dilute Aqueous Solutions Using a Liquid Membrane Process. Hydrometallurgy 1977, 2, 315. (271) Alessi, P.; Canepa, B.; Kikic, I. Influence of Operating Parameters on Selectivity in a Separation Process by Liquid Membrane Permeation for the System Styrene-Ethylbenzene. Can. J. Chem. Eng. 1979, 57, 54. (272) Marr, R.; Kopp, A. Liquid Membrane TechnologysA Review on Phenomena, Transport Mechanisms, and Models. Chem. Ing. Tech. 1980, 52, 399. (273) Schlosser, S.; Kossaczky, E. Comparison of Pertraction through Liquid Membranes and Double Liquid-Liquid Extraction. J. Membr. Sci. 1980, 6, 83. (274) Draxler, J.; Furst, W.; Marr, R. Separation of metal species by emulsion liquid membranes. J. Membr. Sci. 1988, 38, 281. (275) Schuegerl, K.; Mohrmann, A.; Gutknecht, W.; Hauertmann, H. B. Application of Liquid Membrane Emulsion for Recovery of Metals from Mining Wastewaters and Zinc Liquors. Desalination 1985, 53, 197. (276) Boyadzhiev, L.; Sapundzhiev, T.; Bezenshek, E. Modeling of Carrier-Mediated Extraction. Sep. Sci. 1977, 12, 541. (277) Terry, R. E.; Li, N. N.; Ho, W. S. Extraction of Phenolic Compounds and Organic Acids by Liquid Membranes. J. Membr. Sci. 1982, 10, 305. (278) Way, J. D.; Noble, R. D. A Macroscopic Model of a Continuous Emulsion Liquid Membrane Extraction System. In Residence Time Distribution Theory in Chemical Engineering: Proceedings of a Summer School Held at Bad Honnef, August 15-25, 1982; Pethö, Á., Noble, R. D., Eds.; Verlag Chemie: Weinheim, Germany, 1982; pp 247-254. (279) Lorbach, D.; Marr, R. Emulsion Liquid Membranes. Part II: Modelling Mass Transfer of Zinc With Bis(2-Ethylhexyl)Dithiophosphoric Acid. Chem. Eng. Process. 1987, 21, 83. (280) Yurtov, E. V.; Koroleva, M. Y.; Golubkov, A. S.; Grigor’ev, V. B. Structural-Mechanical Barrier in Liquid-Membrane Extraction in a Multiple Emulsion. Dokl. Akad. Nauk SSSR 1988, 302, 1164.

(281) Borwankar, R. P.; Chan, C. C.; Wasan, D. T.; Kurzeja, R. M.; Gu, Z. M.; Li, N. N. Analysis of the Effect of Internal Phase Leakage on Liquid Membrane Separations. AIChE J. 1988, 34, 753. (282) Li, D.; Ma, M. Nanosponges for Water Purification. Clean Technol. EnViron. Policy 2000, 2, 112. (283) Holmberg, K.; Jo¨nsson, B.; Kronberg, B.; Lindman, B. Surfactants and Polymers in Aqueous Solution; John Wiley & Sons: New York, 2003. (284) Thien, M. P.; Hatton, T. A.; Wang, D. I. C. Separation and Concentration of Amino Acids Using Liquid Emulsion Membranes. Biotechnol. Bioeng. 1988, 32, 604. (285) Hersel, U.; Rau, H.; Schnepf, R.; Vetter, D.; Wegge, T. Polymeric Prodrugs Having Temporary Linkages to Amino Groups, World Patent WO 2005099768, 2005. (286) Vetter, D.; Hersel, U.; Rau, H.; Schnepf, R.; Wegge, T. ProteinProteophore Complexes, World Patent WO 2005034909, 2005. (287) Vetter, D.; Rau, H.; Wegge, T.; Hersel, U. Preparation of BicineLinked Polymeric Prodrugs, World Patent WO 2006136586, 2006. (288) Chauhan, A. S.; Svenson, S. Drug Formulations Containing Hybrid Dendrimers, World Patent WO 2007149500, 2007. (289) Demattei, C. R. Delivery of Biologically Active Materials Using Core-Shell Tecto(Dendritic Polymers), World Patent WO 2008054466, 2008. (290) Uhrich, K. E. Hyperbranched Polymeric Micelles for Encapsulation and Delivery of Hydrophobic Molecules, U.S. Patent 6,328,988, December 11, 2001. (291) Brooks, D. E. Polymers Containing Zwitterionic Endgroups, World Patent WO 2008074154, 2008. (292) Hardy, C. T. Biodegradable Triblock Copolymers for Use in Acoustically Mediated Intracellular Drug DeliVery in ViVo, U.S. Patent Application 2008243049, 2008. (293) Carnahan, M. A. Dendritic-Polymer-Based Hydrogels Containing Nanoparticles, World Patent WO 2007005249, 2007. (294) Lion, B. Hyperbranched Polymers Based on (Meth)acrylates for Cosmetics, Eur. Patent EP 1621560, 2006. (295) Prigent, F. Core/Shell Particles Containing Silicone Compounds for Cosmetics and Pharmaceuticals, Fr. Patent FR 2910345, 2008. (296) Simmonet, J.-T.; Biatry, B.; Prigent, F. Core/Shell Type Capsules and Preparation Method, Eur. Patent EP 2011565, 2009. (297) Moore, J. S. Branched and Hyperbranched Polyetherimides, World Patent WO 2000026267, 2000. (298) Ahn, D. Polymer Particles and Encapsulated Compositions Using Organoborane Amine Complexes, World Patent WO 2006088571, 2006. (299) Matsunami, Y. Dendritic Polyurethane Microcapsule and Process for Manufacturing the Same, Eur. Patent EP 1382385, 2004. (300) Malik, N. Preparation of a Dendritic-Platinate Drug Delivery System for Treating Cancerous Tumors, U.S. Patent Application 2002054863, 2002.

ReceiVed for reView February 7, 2009 ReVised manuscript receiVed October 20, 2009 Accepted November 4, 2009 IE900216R

Encapsulation Using Hyperbranched Polymers: From Research and

Recommend Documents