pubs.acs.org/Langmuir © 2009 American Chemical Society
Osmosis Based Method Drives the Self-Assembly of Polymeric Chains into Micro- and Nanostructures Laura Chronopoulou, Ilaria Fratoddi, Cleofe Palocci, Iole Venditti, and Maria V. Russo* Department of Chemistry, University of Rome “La Sapienza”, P.le A. Moro 5, Rome 00185, Italy Received May 8, 2009 Polymers derived from monomers with a variety of functionalities provide materials with a vast range of properties and applications. Worldwide research has recently developed a wide number of methods suitable for the preparation of polymeric materials of nanometric dimensions, in view of the fact that, at the nanoscale level, new and unexpected properties emerge and lead to innovative applications. In this framework, we have exploited an easy method for the generation of nanostructures, regardless of the chemical structure of the pristine amorphous polymers, that is, biopolymers (e.g., polysaccharides) and synthetic, functional, and structural polymers (i.e, polystyrene, polymethylmethacrylates, polyacetylenes, and polymetallaynes). The nanostructure of these macromolecules, considered as the prototypes of various classes of polymeric materials, was achieved by using a simple and versatile procedure based on an osmotic method (OBM). Depending on the choice of solvent/nonsolvent pairs, the dialysis membrane molecular weight cutoff (MWCO), temperature, and polymer concentration, different morphologies can be obtained (e.g., spheres, sponges, disks, and fibers); also, a tuning of the nanoparticle dimensions ranging from the micro- to nanoscale has been obtained.
Introduction Materials with controllable dimensions and shape at the sub-micrometric scale are opening new perspectives in many fields of science and technology.1 In particular, polymeric materials, due to their peculiar characteristics, are of general application in different areas. Synthetic polymers combine lightness, low cost, ease of processing, and functionalization with the characteristic properties of inorganic materials, for example, conductivity,2,3 light propagation,4 linear and nonlinear optical behavior,5 and sensitivity to chemical agents.6 On the other hand, biopolymers, in view of their biocompatibility and biodegradability, are largely employed in biomedicine and pharmacy, for example, tissue engineering,7 diagnostics, and drug delivery,8,9 in the food industry, agriculture, textiles, and in the chemical and packaging industries. Such properties are expected to be enhanced in nanostructured materials. In this context, a simple strategy for nanostructured polymer production is desirable. Nanostructured synthetic polymers are generally obtainable by a variety of chemical approaches, starting from the monomer that is induced to grow polymeric chains which then self-assemble into nanostructured shapes. Several significant examples are briefly outlined hereafter. *Corresponding author. Telephone: þ390649913349. Fax: þ3906490324. E-mail:
[email protected]. (1) Satyanarayana, V. N. T.; Kuchibhatla, A. S. K.; Debasis, B.; Seal, S. Prog. Mater. Sci. 2007, 52, 699–913. (2) Lee, K.; Cho, S.; Park, S. H.; Heeger, A. J.; Lee, C.-W.; Lee, S.-H. Nature 2006, 441, 65–68. (3) Salleo, A. Mater. Today 2007, 10, 38–45. (4) Pursiainen, O. L.; Baumberg, J. J.; Winkler, H.; Viel, B.; Spahn, P.; Ruhl, T. Opt. Express 2007, 15, 9553–9561. (5) Kippelen, B. Springer Ser. Opt. Sci. 2007, 114, 487–534. (6) McQuade, D. T.; Pullen, A. E.; Swager, T. M. Chem. Rev. 2000, 100, 2537–2574. (7) Biondi, M.; Ungano, F.; Quaglia, F.; Netti, P. A. Adv. Drug Delivery Rev. 2008, 60, 229–242. (8) Heath, F.; Haria, P.; Alexander, C. AAPS J. 2007, 9, E234–240. (9) Payne, G. F. Curr. Opin. Chem. Biol. 2007, 11(2), 214–219.
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Considering a widely studied polymer, polyaniline, nanotubes, nanofibers, nanorods, and hollow microspheres have been synthesized by electrochemical routes, using acids as oxidants, with the aid of templates and by self-assembly approaches.10-17 Emulsion polymerization is one of the most common methods that allow the preparation of nanosized polymer particles, whose principles concerning kinetics and mechanisms have been recently reported.11,12 This method usually requires the use of surfactants which might constitute an additional cost and pollute the product, though the development of controlled radical polymerization methods and surfactant-free emulsion polymerization is gradually overcoming this issue.13,14 A different approach is based on microwave preparation of cross-linked nanopolymers,15 and another simple method that uses routine laboratory chemicals and equipment allows one to generate precisely shaped polystyrene and polyvinyl alcohol micro- and nanoparticles.16 Elecrospinning is also a widely used and versatile technique for the preparation of polymeric nanofibers, which are suitable for the incorporation of biological molecules, cells, or other nanoparticles.17 Moreover, recent approaches use self-assembly at liquidliquid interfaces to drive nanoparticle formation, opening to new industrial applications. For example, self-assembled nanoparticles at a liquid-liquid interface serve as building blocks for (10) Wan, M. X. In Encyclopedia of Nanoscience and Nanotechnology; Nalwa, H. S., Ed.; American Scientific Publishers: Los Angeles, 2004; Vol. 2, pp 153-169. (11) Thickett, S. C.; Gilbert, R. G. Polymer 2007, 48, 6965–6991. (12) Capek, I. Adv. Colloid Interface Sci. 2002, 99, 77–162. (13) Voccia, S.; Ignatova, M.; Jerome, P.; Jerome, C. Langmuir 2006, 22, 8607–8613. (14) Ngai, T.; Wu, C. Langmuir 2005, 21, 8500–8525. (15) An, Z.; Tang, W.; Hawker, C. J.; Stucky, G. D. J. Am. Chem. Soc. 2006, 128, 15054–15055. (16) Champion, J. A.; Katare, Y. K.; Mitragotri, S. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 11901–11904. (17) Ramakrishna, S.; Fujihara, K.; Teo, W.-E.; Lim, T.-C.; Ma, Z. An Introduction to Electrospinning and Nanofibers; World Scientific Publishing Co. Pte. Ltd.: Singapore, 2005.
Published on Web 07/02/2009
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Chart 1. Chemical Structures of Synthetic and Biopolymers: Polymethylmethacrylate (PMMA), Polystyrene (PS), Polyacetylenes (PA: PPA, PDMPA, PDMPAHCl), Polymetallaynes (MPy: Pt-DEBP, Pd-DEBP), Hyaluronic Acid Derivatives (HYAFFs: HYAFF9, HYAFF11), Chitosan (CS), Pullulan (PU), and Dextran (DX)
the achievement of new functional materials with unique physical properties.18-20 Owing to their peculiar structures, most nanostructured biopolymers cannot be produced by “bottom-up” procedures. In those cases, a “top-down” approach must be used, starting from the macrometric polymer itself. The bioadhesive and self-assembling abilities of biopolymeric materials are exploited in a versatile approach for the nanofabrication of different biohybrids based on interactions between inorganic and biomaterials, for example, silica and biopolymers.21,22 Methods for preparing polysaccharide based micro- and nanoparticles rely on a variety of approaches including interactions with counterions, chemical cross-linking, solvent evaporation, coating on preformed microparticles, and spray-drying.23 In the present work, we have focused our research on a range of synthetic and natural, functional, and structural polymers and we (18) Chen, H.; Dong, S. Langmuir 2007, 23, 12503–12507. (19) Deng, Z.; Peng, B.; Chen, D.; Tang, F.; Muscat, A. J. Langmuir 2008, 24, 11089–11095. (20) Luo, M.; Mazyar, O. A.; Zhu, Q.; Vaughn, M. W.; Hase, W. L.; Dai, L. L. Langmuir 2006, 22, 6385–6390. (21) Masciangioli, T.; Zhang, W. X. Environ. Sci. Technol. 2003, 37, 102A–108A. (22) Palocci, C.; La Grotta, A.; Barbetta, A.; Dentini, M. Langmuir 2007, 23, 8243–8245. (23) Sinha, V. R.; Singla, A. K.; Wadhawan, S.; Kaushik, R.; Kumria, R.; Bansal, K.; Dhawan, S. Int. J. Pharm. 2004, 274, 1–33. (24) Palocci, C.; Russo, M. V.; Belsito, C. M. A.; Cernia, E.; D’Amato, R.; Fratoddi, I.; Panzavolta, F.; Soro, S.; Venditti, I. PCT/IT20057000653 International Publication Number WO 2006-051572 A3.
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have developed an osmosis based method (OBM)24 that is simple and versatile for the control of both dimension and morphology of polymeric materials at the sub-micrometric scale via selfassembly. This method is of general application and proved to be suitable for both synthetic and biopolymers.
Experimental Section Materials. Dialysis cellulose membranes (cellulose acetate,
33 21 mm, MWCO = 12 and 2 KDa) were purchased from Aldrich. Reagent grade solvents (DMF, DMSO, EtOH, MeOH, CHCl3, THF) were used without further purification. PMMA and PS were purchased from Aldrich. Amorphous PPA was prepared and characterized according to our previous studies25 as well as amorphous PDMPA and PDMPAHCl,26 and Pt-DEBP and Pd-DEBP.27 The biopolymers dextran (DX), pullulan (PU), and chitosan (CS) were purchased from Sigma-Aldrich. Hyaluronic acid derivatives, HYAFF 11 p100 and HYAFF 9 p75, were provided by Fidia pharmaceuticals. See Chart 1 for structures of synthetic and biopolymers. OBM Method. The polymer under test was dissolved in a suitable solvent (the concentration was chosen depending upon the desired kind of nanomorphology), and the solution (usually (25) Furlani, A.; Napoletano, C.; Russo, M. V.; Camus, A.; Marsich, N. J. Polym. Sci., Part A: Polym. Chem. 1989, 27, 75–86. (26) Russo, M. V.; Furlani, A.; Polzonetti, G.; Altamura, P.; Fratoddi, I. Polymer 1997, 38, 3677–3690. (27) Fratoddi, I.; Gohlke, C.; Cametti, C.; Diociaiuti, M.; Russo, M. V. Polymer 2008, 49, 3211–3216.
DOI: 10.1021/la9016382
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Article Scheme 1. Schematic Representation of the OBM Method
10 mL) was transferred into a dialysis bag and further immersed into the selected nonsolvent (usually 200 mL). A schematic representation of the process is shown in Scheme 1. The solvent and the nonsolvent must be miscible, and a nominal v/v solvent/ nonsolvent volume ratio = 1/20 was chosen for the application of the OBM method. The procedure was carried out at constant temperature (T = 4 °C or T = 25 °C was adopted). Precipitation of the nanoparticles occurs at times that are dependent on the experimental conditions (nature of the polymer, solvent/nonsolvent pair, temperature, MWCO of the membrane). After 72-96 h (osmotic equilibrium was reached), the polymer suspension was recovered, centrifuged twice after suspension into a nonsolvent, and cast deposited onto a corn glass substrate for the SEM investigation.
Procedure for the Production of Different Morphologies of Polymers. PMMA, PS, PPA, PDMPA, PDMPAHCl, Pt-DEBP, Pd-DEBP, and HA derivatives (0.1-25 mg/mL) were dissolved in an organic solvent; DX and PU (0,1-1 mg/mL) were dissolved in distilled water (pH = 6.5), and CS (0.1 mg/mL) was dissolved in distilled water acidified with acetic acid (pH = 5.5). The dialysis bag (cellulose acetate, MWCO = 12 000 and 2000 Da) containing the polymer solution was then immersed in the selected nonsolvent (solvent/nonsolvent ratio, v/v 1/20) until thermodynamic equilibrium was reached (48-72 h). The precipitated polymers were recovered, washed several times with the nonsolvent, and freeze-dried. GPC and 1H NMR measurements were performed on synthetic polymers before and after being processed by OBM, in order to verify the polymers’ structural integrity (data shown in the Supporting Information). 1H NMR measurements were also performed on biopolymers, proving that OBM does not involve any structural changes in the materials. Instruments. A Leo 1450 instrument was used for scanning electron microscopy (SEM) on polymeric films cast or spin deposited from different solvents (H2O, CHCl3, DMF, toluene, EtOH) on gold or glass substrates. Evaporation rates were controlled by carrying out depositions of the samples in controlled temperature and relative humidity chambers. The particle size distribution is expressed by the ratio Dw/Dn, namely, the polydispersity index (PI). Dw and Dn are the weight 11942 DOI: 10.1021/la9016382
Chronopoulou et al. average diameter and the number average diameter of particles, respectively, and they were calculated on 100 measurements performed on the same sample with the aid of the Scion image software directly on the SEM images.28
Results and Discussion OBM: General Features. The OBM is based on the use of a physical barrier, specifically dialysis membranes or common semipermeable membranes that allow the passive transport of solvents to slow down the mixing of a polymer solution with a nonsolvent; the dialysis membrane contains the solution of the polymer. The gradual mixing of the solvent and the nonsolvent inside the bag causes the mixture to be progressively less able to dissolve the polymer. The consequent increase in interfacial tension drives the molecules of the polymer to aggregate into spheroidal particles; their resultant shape allows a minimization in energy of the system, and hence, a precipitation occurs. In some cases, nanostructured rods and fibers are obtained depending on the physicochemical conditions of the system. The advantages of the method, in addition to low cost and general applicability, are manifold: the procedure is conducted under mild conditions, avoiding the use of emulsifiers and costabilizers, pure products are obtained, and solvents are easily recovered by distillation. After centrifugation and subsequent drying of the polymer suspension, polymer yields are almost quantitative. Moreover, the method permits the nanoparticle formation simultaneously with the bioactive molecule immobilization.29 For example, molecules with biological activity (enzymes, nucleic acids, drugs, etc.) are expected to be linked to nanostructured polymers either with noncovalent or with covalent bonds, depending on the matching of the functional groups of the biomolecule with the selected polymer.30 The speed of solvent mixing could be one of the factors that modulate the product morphology as a function of several parameters, among them the solvent/nonsolvent pair, the dialysis membrane molecular weight cutoff (MWCO), the temperature at which the process is carried out, and the polymer concentration. According to well established statements reported in the literature, the morphology of the particles is then determined by kinetic and thermodynamic factors.31 From a thermodynamic viewpoint, the most important parameter is the free interface energy.32 When the precipitation process is slow enough, the morphology is not influenced by the kinetic parameters and the so-called equilibrium morphology is reached, corresponding to the minimization of the free energy of the system. The kinetic parameters mainly affecting the particle morphology are the diffusion and the phase rearrangement inside the particles themselves. The mobility of polymeric chains is restricted during their aggregation, and hence, phase separation and rearrangement can be slower than the aggregation rate. When kinetic factors prevail over thermodynamic ones, nonequilibrium morphologies are obtained. The morphologies obtained by our OBM can be modulated in a variety of shapes: spongy, tubular rods (nonequilibrium morphologies) and spheres with dimensions ranging between micrometers and nanometers, depending on the experimental (28) Chen, C.-W.; Serizawa, T.; Akashi, M. Chem. Mater. 1999, 11, 1381– 1389. (29) Masotti, A.; Bordi, F.; Ortaggi, G.; Marino, F.; Palocci, C. Nanotechnology 2008, 19, 055302–055307. (30) Palocci, C.; Chronopoulou, L.; Venditti, I.; Cernia, E.; Diociaiuti, M.; Fratoddi, I.; Russo, M. V. Biomacromolecules 2007, 8, 3047–3053. (31) Stubbs, J. M.; Sundberg, D. C. J. Appl. Polym. Sci. 2004, 9, 1538–1551. (32) Evans, D. F.; Wennerstrom, H. The Colloidal Domain: Where Physics, Chemistry, Biology and Technology Meet; Wiley-VCH: New York, 1999; pp 1-632.
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Figure 1. SEM images of morphologies obtained for synthetic polymers (A, PMMA; B, PS; C, PPA; D, PDMPAHCl; E, PDMPA; F, Pt-DEBP) and biopolymers (G, CS; H, I, L, M, HYAFF9; N, DX). For experimental conditions, see Table 1. Table 1. OBM Experimental Conditions for the Achievement of Natural and Synthetic Polymers Nano- and Microstructures polymer or biopolymer
SEM image
T (°C)
solvent pair
conc [mg/mL]
morphology
mean particle size (nm)
PIa
PMMA PS PPA PDMPAHCl PDMPA Pt-DEBP CS HYAFF9 HYAFF9 HYAFF9 HYAFF9 DX
A B C D E F G H I L M N
4 25 25 25 25 25 4 4 4 4 4 4
acetone/H2O DMF/H2O DMF/H2O THF/H2O THF/H2O CHCl3/EtOH CH3CN/H2O H2O/EtOH H2O /MeOH DMSO/MeOH H2O/acetone H2O/EtOH
5 5 10 1 1 1 0.5 0.5 0.5 0.5 0.5 0.5
spheres sponge spheres fibers spheres spheres disks flowerlike spheres spheres dandelion-like spheres
200-2000 500 100-300 1000-3000; L = 10 μmb 800-1600 200-400 2000-3000 2000-3000 500-600 300-400 8000-10000 200-1000
1.13
a
1.11 1.92 1.88 1.00 1.50 1.14
PI = polydispersity index, calculated for spherical particles as in the Experimental Section. b L = fiber length.
conditions. Typical examples of micro/nanomorphologies obtained in this work with the OBM procedure are reported in Figure 1 with the appropriate data collected in Table 1. Langmuir 2009, 25(19), 11940–11946
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Figure 2. Diameter-concentration profiles for spheres of polymers by OBM procedure. (A) PMMA: solvent=acetone, T=4 °C ; (B) PMMA: solvent=DMF, T=25 °C; (C) PPA: solvent=DMF, T=4 and 25 °C. Error bars are calculated as the product of PI 100 for a graphical representation.
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Figure 4. SEM images of nanostructured PS obtained in different experimental conditions: (A) DMF/MeOH, 1.5 mg/mL, T = 25 °C; (B) DMF/MeOH, 1.5 mg/mL, T=4 °C; (C) DMF/MeOH, 3 mg/mL, T=4 °C.
solvent/nonsolvent pairs, and molecular weight membrane cutoff. Effect of Concentration and Temperature on Nanoparticle Size. We have earlier studied the emulsion polymerization of PMMA leading to nanospheres with diameters in the range 100-400 nm and very low polydispersion.33 In the present work, a systematic study of the experimental conditions for the formation of nanospheres by a different route was carried out. By using the OBM procedure, a linear correlation between polymer concentration and the diameter of the nanospheres was observed in the range 100-1000 nm (see Figure 2A and B). Figure 3. SEM images of sub-micrometric structures of Pd-DEBP (experimental conditions: CHCl3/MeOH 1 mg/mL, T = 4 °C). 11944 DOI: 10.1021/la9016382
(33) D’Amato, R.; Venditti, I.; Russo, M. V.; Falconieri, M. J. Appl. Polym. Sci. 2006, 102, 4493–4499.
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Figure 5. Schematic representation of the dependence of the PPA morphology from Δε of the solvent pair at T=25 °C: (A) DMF/hexane,
Δε = 34, c = 5 mg/mL; (B) DMF/H2O, Δε = 42, c = 10 mg/mL; (C) acetone/H2O, Δε = 58, c = 0.5 mg/mL; (D) THF/H2O, Δε = 72, c=0.5 mg/mL (dimension bar=1 μm).
Figure 6. Schematic representation of the dependence of the morphology from Δε of the solvent pair. (Top) HYAFF 11, c=0. 5 mg/mL, T = 4 °C: (A) DMSO/MeOH, Δε = 14.2; (B) DMSO/EtOH, Δε = 22.9; (C) DMSO/H2O, Δε = 32.8 (dimension bar: A = 2 μm; B=200 nm ; C=1 μm). (Bottom) HYAFF 9, c=0. 5 mg/mL, T=4 °C: (D) DMSO/MeOH, Δε=14.2; (E) DMSO/EtOH, Δε=22.9; (F) H2O/MeOH, Δε=47.
In the case of PPA, the diameter of the nanospheres versus concentration is shown in Figure 2C, in a concentration range lower with respect to PMMA, due to lower solubility of PPA. At low concentrations (1 mg/mL or less), lower temperature leads to the formation of nanoparticles with smaller diameters than those obtained at room temperature. This is probably due to the formation of many nucleation centers in a fast precipitation process that occurs at higher temperatures. At higher concentrations, the influence of the temperature on the dimensions seems to be less effective. Nanosized Pt-DEBP spheres could also be formed by the straightforward osmosis procedure (see Figure 1F) with diameters in the range 200-600 nm, using as solvent pair CHCl3/EtOH. The formation of spongelike structures was observed by using higher polymer concentrations; superimposed structures based on spheres with a diameter of about 60 nm were obtained by varying the metal center, that is, Pd(II) in the polymetallayne chemical structure (Figure 3). In conclusion, by varying the experimental conditions such as temperature and concentration, parameters that influence the precipitation rate, different morphologies, and size modulation can be obtained. For example, in the case of PS, if all the parameters are kept constant, a temperature decrease induces Langmuir 2009, 25(19), 11940–11946
a decrease of the nanosphere diameter (see Figure 4A, B); when the concentration increases, a growth in diameter is observed (see Figure 4B, C). Natural biopolymers (PU, DX, HYAFFs) were submitted to OBM at 4 and 25 °C using a fixed polymer concentration. Amorphous morphologies were obtained when the polymers were processed at 25 °C, whereas at 4 °C different nanostructures were observed (see Figure 1M and N for DX and HYAFF9, respectively). Effect of the Solvent/Nonsolvent Pair. Since the precipitation depends, among other parameters, on the chemical properties of the solvent/nonsolvent pair, a correlation between morphology and solvents Δε (difference between the dielectric constant values of the solvent/nonsolvent pair) was studied. While the concentration mainly tunes the size of the spheres, as described in the previous paragraph, a systematic variation of Δε affects both shape and size, and structures of various morphologic features can be achieved. Considering a completely hydrophobic and apolar polymer such as π-conjugated PPA, a decrease of Δε leads to the formation of big spheres (Figure 5A, B), whereas an increase of this parameter induces the formation of spongelike nanostructures. (Figure 5C and D). DOI: 10.1021/la9016382
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biopolymers. Therefore, when the polymer and the solvent/ nonsolvent mixture have similar polarity, the equilibrium morphology is favored. Influence of the MWCO on Nanostructured Polymer Dimensions. With the aim to evaluate the influence of physical parameters on the polymer nanostructure dimensions, we used dialysis bags with different MWCOs. Aqueous solutions of PU, DX, and CS were submitted to OBM by using dialysis membranes with MWCOs of 12 000 and 2000 Da. Figure 7 reports the SEM micrographs of (A) DX, (B) PU, and (C) CS micro- and nanospheres. Reducing the membrane MWCO, the mean diameter of the spheres decreases by about 2 orders of magnitude, ranging from 1.5 μm (MWCO = 12 000 Da) to 20-30 nm (MWCO = 2000 Da). These experimental results confirm the importance of the mixing rate of the solvent pairs inside the dialysis bag in determining the final equilibrium morphology. By reducing the membrane MWCO, the mixing rate of the solvents decreases, thus favoring thermodynamic factors over kinetic ones in the organization of polymeric chains. The evaluation of the influence of MWCO was carried out for the synthetic polymer PPA at different concentrations of the polymer in DMF (0.5 and 0.1 mg/mL). The decrease of the membrane pore diameters induces a decrease of the mean particle diameter, in the range 80-100 nm, in analogy to the results obtained for biopolymers.
Figure 7. SEM micrographs of nanostructured biopolymers. (A) DX: H2O/EtOH, 0.5 mg/mL, MWCO 12 000; (B) DX: H2O/ EtOH, 0.5 mg/mL, MWCO 2000; (C) PU: H2O/EtOH, 1 mg/mL, MWCO 12 000; (D) PU: H2O/EtOH, 1 mg/mL, MWCO 2000; (E) CS: H2O/EtOH, 0.5 mg/mL, MWCO 12 000; (F) CS: H2O/EtOH, 0.5 mg/mL, MWCO 2000.
Applying the OBM procedure and varying the solvent/nonsolvent pair (CHCl3/hexane Δε = 2.9 or THF/H2O Δε = 72.5) for PDMPA, a conjugated polymer containing polar pendant groups with different morphologies was also obtained. Submicrometric grains change their morphology, and spheres are obtained by increasing the Δε between solvent and nonsolvent pairs (images in the Supporting Information). The effect of the variation of Δε was then extended to biopolymers. Hydrophilic and polar HA derivatives, (HYAFF11 and HYAFF9) were investigated, and their behavior is reported in Figure 6, where a variation of the sub-micrometric structure can be observed: increasing the value of Δε, the formation of spheres (micro and nano) is favored for both biopolymers. CS was processed with OBM employing different solvent/ nonsolvent pairs: H2O/EtOH (Δε = 55.7), H2O/acetone (Δε = 59.3), and H2O/THF (Δε = 72.48); the images of the resulting micro/nanostructures are not reported; as observed in the case of HYAFFs, and in general for polymers with polar groups, also for CS, the increase of the Δε leads to the preferential formation of spheres when THF is used as the nonsolvent (increase of Δε). The above-reported results suggest that, for polymers of low polarity, a decrease of the solvent/nonsolvent mixture polarity favors the formation of spheres. The opposite trend is found for polymers containing highly polar groups, that is,
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Conclusions A novel and straightforward strategy to fabricate nanostructured polymers by exploiting their solution properties at the interface in different media is presented. Variations of the polymer morphologies and size modulation can be obtained by changing the experimental conditions of the OBM process such as temperature, polymer concentration, solvent polarity, and dialysis membrane molecular weight cutoff. These physicochemical parameters are able to control the osmotic process, thus influencing polymer nucleation during nanostructure formation. Spherical morphologies can be easily obtained by controlling temperature and polymer concentration or by changing the dielectric constant difference between the solvent and nonsolvent. Other nonequilibrium morphologies are obtained, although their formation cannot be precisely foreseen through the control of all the physicochemical parameters. The nanoparticles obtained are free of contaminants such as surfactants, initiator residues, and their decomposition products. The methodology proposed can be applicable to a broad range of polymers including those which cannot be obtained by emulsion polymerization (biopolymers). Finally, the modulation in shape and dimensions of the nanostructured materials opens new strategies for application in biotechnology and sensing areas. Acknowledgment. The authors thank Dr. Daniela Ferro for SEM images, Fidia Pharmaceuticals for providing hyaluronic acid derivatives, HYAFF 11 and HYAFF 9, and Dr. Peter Preston for valuable advice and language revision. Supporting Information Available: NMR and GPC data for polymers before and after OBM method and SEM images. This material is available free of charge via the Internet at http://pubs.acs.org.
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