Article pubs.acs.org/JAFC
Preparation of Starch Nanoparticles in a Water-in-Ionic Liquid Microemulsion System and Their Drug Loading and Releasing Properties Gang Zhou, Zhigang Luo,* and Xiong Fu* Carbohydrate Laboratory, College of Light Industry and Food Science, South China University of Technology, Guangzhou 510640, China ABSTRACT: An ionic liquid microemulsion consisting of 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF6), surfactant TX-100, 1-butanol, and water was prepared. The water-in-[Bmim]PF6 (W/IL), bicontinuous, and [Bmim]PF6-in-water (IL/W) microregions of the microemulsion were identified by conductivity measurements. Starch nanoparticles with a mean diameter of 91.4 nm were synthesized with epichlorohydrin as cross-linker through W/IL microemulsion cross-linking reaction at 50 °C for 4 h. Fourier transform infrared spectroscopy (FTIR) data demonstrated the formation of cross-linking bonds in starch molecules. Scanning electron microscopy (SEM) revealed that starch nanoparticles were spherical and that some particles showed aggregation formation. Furthermore, drug loading and releasing properties of starch nanoparticles were investigated with mitoxantrone hydrochloride as a drug model. This work provides an efficient and environmentally friendly approach for the preparation of starch nanoparticles, which is beneficial to their further application. KEYWORDS: ionic liquid microemulsion, cross-linking, starch nanoparticles, drug loading, drug release
■
INTRODUCTION Starch, one of the most abundant natural polymers, is renewable, biodegradable, and modifiable. However, native starches have limitations such as poor processability and solubility, which limit their industrial application. Therefore, starches have been modified for many years through physical, chemical, or enzymatic processes to improve their properties.1,2 Among various modifications, cross-linked starch microspheres show good properties, such as high stability toward swelling, high shear, high temperature, and acidic conditions.3 Besides, cross-linked starch microspheres possess good performance in biodegradability, nontoxicity, stability during storage, and costeffectiveness as well as simple fabrication method.4 In view of the good properties, cross-linked starch microspheres can be used in many areas, especially in drug delivery systems as a drug carrier.5 Several years ago, Malafaya et al.6 prepared cross-linked starch microspheres and studied their loading properties to biologically active agents. Some researchers found that crosslinked starch microspheres are promising vehicles in the intranasal drug delivery system.7,8 In addition, starch microspheres have also been used as drug carriers for the treatment of liver cancer or arterial embolism via parenteral route.9−12 As we know, the applications of starch microspheres in drug delivery systems are influenced by their particle size and administration route. However, the literature about the preparation of cross-linked starch microspheres shows that they possess relatively large size and broad size distribution.13 Therefore, the quality of starch microspheres is desperately expected to be improved for better application. Starch microspheres have been synthesized through several approaches, among which the water-in-oil (W/O) emulsion cross-linking technique has been widely used because of the defined and simple preparation steps with mild processing conditions.14 However, the W/O emulsion cross-linking © 2014 American Chemical Society
technique requires a lot of toxic organic reagents, which will influence the quality of starch microspheres and lead to pollution, and starch microspheres obtained from this approach still appear relatively big in size and have a wide size distribution range.15 Heretofore, there are few reports of the synthesis of starch nanoparticles by the emulsion cross-linking method. Shi et al.14 prepared starch nanoparticles in a traditional W/O microemulsion system with a volume ratio of oil to water at 15:2. In view of the fact that a lot of toxic organic reagents are used in this traditional microemulsion, it is essential to develop an environmentally friendly emulsion cross-linking method for the synthesis of starch nanoparticles. Room temperature ionic liquids (ILs) have become more and more important as desirable green solvents and reaction media due to their recyclability and designability.16 Recently, many documents have shown that ILs can substitute polar phase, nonpolar phase, or surfactant to prepare ionic liquid microemulsions, and some inorganic nanomaterials can be prepared in this kind of system.17−21 However, only Zhou et al.22 performed the synthesis of starch nanoparticles through an ionic liquid-in-oil (IL/O) microemulsion technique, and the achieved starch nanoparticles possessed an average diameter of 96.9 nm. In this paper, ionic liquid 1-octyl-3-methylimidazolium acetate substituted for the water phase and cyclohexane served as oil phase. Therefore, this IL/O microemulsion system was not environmentally friendly because of the use of toxic organic reagents such as cyclohexane. To explore an efficient and environmentally friendly approach for the preparation of starch nanoparticles, we Received: Revised: Accepted: Published: 8214
April 18, 2014 July 27, 2014 July 28, 2014 July 29, 2014 dx.doi.org/10.1021/jf5018725 | J. Agric. Food Chem. 2014, 62, 8214−8220
Journal of Agricultural and Food Chemistry
Article
substituted the oil phase with [Bmim]PF6 and prepared a water-in-ionic liquid (W/IL) microemulsion. Furthermore, the oil phase substituted by [Bmim]PF6 in the W/IL microemulsion was much less than that in the W/O microemulsion and IL/O microemulsion, suggesting that the W/IL microemulsion was a green system. In this work, we investigated the synthesis of starch nanoparticles in a W/IL microemulsion system. Starch nanoparticles with small size and narrow size distribution were successfully obtained and characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic light scattering (DLS). Moreover, drug loading and releasing properties of starch nanoparticles were investigated with mitoxantrone hydrochloride as a drug model. This work provided an efficient and environmentally friendly approach for the preparation of starch nanoparticles and may be beneficial to the further applications of starch nanoparticles in many fields.
■
Figure 1. Scheme of microemulsion cross-linking reaction of starch. the W/IL microemulsion with the aid of 40 g of a mixture of surfactant TX-100 and cosurfactant 1-butanol (TX-100/1-butanol = 3:1, w/w). After several minutes of magnetic stirring, epichlorohydrin (1.84 g) was added to the above microemulsion as a cross-linker. In this stage, the mixture was stirred by a DF-II thermostatic magnetic stirring apparatus at the speed of 1200 rpm at 50 °C for 4 h. Subsequently, the reaction solution was cooled to room temperature, and starch nanoparticles were precipitated with methanol under vigorous stirring followed by centrifugation. The precipitate was washed thoroughly with sufficient methanol and ethanol to eliminate [Bmim]PF6, unreacted epichlorohydrin, 1-butanol, and TX-100. Finally, the solid was centrifuged and dried in a vacuum at 45 °C for 24 h. Characterization of Starch Nanoparticles. The structure character of acid-treated granular starch and starch nanoparticles was analyzed by a Nicolet 510 spectrophotometer (Thermo Electron Corp., Waltham, MA, USA) using the KBr disk technique. For FTIR measurement, the samples were mixed with anhydrous KBr and then compressed into thin disk-shaped pellets. The spectra were obtained with a resolution of 2 cm−1 over a wavenumber range of 400−4000 cm−1. SEM images of acid-treated granular starch and starch nanoparticles were examined by means of a model 430 scanning electron microscope (FEI Corp., Hillsboro, OR, USA). The samples were mounted on an aluminum stub with double sticky tape, followed by coating with gold in a vacuum before examination. The accelerating voltage was 5 kV. The size distribution of starch nanoparticles was determined by DLS. Before measuring, 0.1 g of starch nanoparticles was added to 100 mL of distilled water and treated by ultrasound for 30 min to disperse sufficiently. Standard Curves of Mitoxantrone Hydrochloride. Standard curves of mitoxantrone hydrochloride in phosphate-buffered saline (PBS, 0.2 mol/L, pH 7.4) were obtained using the following approaches: 0.01 mg/mL of mitoxantrone hydrochloride in PBS solution was scanned at wavelengths between 360 and 760 nm with a model TU-1810 ultraviolet−visible spectrophotometer (Beijing Puxi General Apparatus Co., Ltd., Shanghai, China). The wavelength at which mitoxantrone hydrochloride absorbed the most was selected as the testing wavelength for later experiments. Then, 0.0025, 0.005, 0.01, 0.02, 0.03, and 0.04 mg/mL of mitoxantrone hydrochloride in PBS solution were measured at the corresponding testing wavelengths to obtain the standard curve of mitoxantrone hydrochloride absorbance to concentration. Drug Loading Analysis. About 50 mg of starch nanoparticles with diameters of 64, 176, and 255 nm were weighed and suspended in 10 mL of PBS solution with 0.0221, 0.0442, 0.0884, and 0.1326 mg/mL mitoxantrone hydrochloride each. The resulting suspensions were gently stirred at the desired temperature of 17, 27, 37, and 47 °C for 0.5, 1, 1.5, 2, 2.5, and 3 h. Subsequently, the solutions were centrifuged, and each supernatant was extracted to determine the drug loading and encapsulation efficiency with an ultraviolet−visible spectrophotometer according to the standard curve of mitoxantrone hydrochloride absorbance to concentration. The drug loading (A) and
MATERIALS AND METHODS
Materials. Acid-treated granular starch was obtained from Guangzhou Chemical Reagent Factory (Guangzhou, China). 1Butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF 6 , >99%) was purchased from Lanzhou Institute of Chemical Physics (Lanzhou, China). Mitoxantrone hydrochloride was provided by Hubei Jianyuan Chemical Co., Ltd. (Wuhan, China). All other chemicals were of analytical grade. Preparation of Ionic Liquid Microemulsions. The preparation of a water/Triton X-100 (TX-100) + 1-butanol/[Bmim]PF6 system was conducted by direct visual observation. First, certain amounts of water and [Bmim]PF6 were added into a small beaker, and their masses were determined by an FA1104N analytical balance (Shanghai Balance Instrument Co., Shanghai, China) with a resolution of 0.0001 g. The temperature was controlled by a DF-II thermostatic magnetic stirring apparatus (Shanghai Yuzheng Instrument Co., Shanghai, China). After thermal equilibrium, the mixture of TX-100 and 1butanol with the mass ratio of TX-100 to 1-butanol at 3:1 was added into the solution until the hierarchical and hazy liquid solution became transparent, which was indicative of the formation of the single phase. Phase Diagram Determination. The pseudoternary phase diagram of the microemulsion was determined at 25 °C as described above. A series of microemulsions were prepared through changing the mass ratio of [Bmim]PF6/water at 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, and 1:9, respectively. The corresponding composition of the solution was noted as the phase boundary. Conductivity Measurements. Conductivity measurements were taken with a model DDSJ-308A conductometer (Shanghai Precision Scientific Instrument Co., Shanghai, China) at 1 kHz using a dip-type cell of cell constant 0.971 cm−1. The errors in the conductance measurements were ±0.5%. The water was progressively added to the mixture of [Bmim]PF6, TX-100, and 1-butanol, and the conductance was measured after thorough mixing and temperature equilibration. Dynamic Light Scattering. DLS is used to determine the size distribution of microemulsions and further demonstrate the formation of W/IL microemulsions. Measurements were conducted using a Malvern Nano-Zetasizer particle size analyzer (Malvern Instrument Ltd., Worcestershire, UK) at a wavelength of 633 nm. The scattering angle was set at 90°. Samples were maintained at 25.0 °C during the experiments. Preparation of Starch Nanoparticles. Starch nanoparticles were prepared according to the W/IL microemulsion cross-linking method with epichlorohydrin as a cross-linker. This method combined the ionic liquid microemulsion with cross-linking reaction of starch nanoparticles. The solidification of the starch molecules and crosslinking reaction took place during the stable W/IL microemulsion. The reaction scheme for cross-linked starch nanoparticles is depicted in Figure 1. First, the aqueous phase was prepared by dissolving acidtreated granular starch (0.5 g) in 9.5 g of NaOH solution (NaOH/ H2O = 1:50, w/w) and then poured into [Bmim]PF6 (40 g) to form 8215
dx.doi.org/10.1021/jf5018725 | J. Agric. Food Chem. 2014, 62, 8214−8220
Journal of Agricultural and Food Chemistry
Article
encapsulation efficiency (B) were calculated with eqs 1 and 2, respectively.
A = (C0 − nC1)V0/W
(1)
B = C0 − nC1/C0
(2)
region, the IL (or oil)-in-water microemulsion region, and the bicontinuous region.17,24 In our research, the W/IL microemulsion was chosen as the cross-linking reaction system. Therefore, it is essential to investigate the structure of this kind of microemulsion. Conductivity measurement is commonly used to locate the subregions of microemulsions.24 Figure 3
C0 means initial concentration of mitoxantrone hydrochloride in PBS, C1 means diluted concentration of mitoxantrone hydrochloride in PBS, n means dilution multiple of extracted supernatant, V0 means initial volume of mitoxantrone hydrochloride in PBS, and W means the weight of starch nanoparticles dissolved in PBS. Drug Release Analysis. About 90 mg of drug-loaded starch nanoparticles that possess the most drug loading (1.5587 mg/g) under the experimental conditions above was weighed and added to the dialysis tube. Then, 10 mL of PBS solution was added to the dialysis tube. Subsequently, the drug-loaded starch nanoparticles and dialysis tube were placed in a beaker containing 80 mL of PBS solution and slowly stirred in magnetic stirring apparatus at 37 °C. At appropriate time intervals, 5 mL of solution was taken out and replaced by the same volume of fresh PBS solution. The cumulative release rate was determined according to the standard curve of mitoxantrone hydrochloride absorbance to concentration and eq 3. R = M1/M 0
(3)
M1 is the cumulative mass of mitoxantrone hydrochloride released from drug-loaded starch nanoparticles at a given time, and M0 is the total drug loading in starch nanoparticles.
Figure 3. Conductivity as a function of weight fraction of water in the microemulsions at 25 °C with the mass ratio of [Bmim]PF6 to TX-100 + 1-butanol at 1:4.
RESULTS AND DISCUSSION Phase Diagram. A phase diagram is useful for further characterizing the microemulsions and choosing the proper cross-linking reaction system. The phase diagram of the water/ TX-100 + 1-butanol/[Bmim]PF6 system at room temperature is shown in Figure 2. Apparently, two different regions, a two-
illustrates the dependence of the conductivity on the weight fraction of water with the mass ratio of [Bmim]PF6 to TX-100 + 1-butanol at 1:4. Obviously, it could be seen that the conductivity increased first and then decreased with an increase in water content, representing the subregion structure transition from W/IL to IL/W after passing through a bicontinuous region (B), indicative of the existence of three subregions. A similar phenomenon could also be seen in ethylene glycol/TX-100/[Bmim]PF6 microemulsions.25 Size Distribution of Microemulsions. The size distribution of the droplets in the W/IL microemulsions was characterized by DLS. In this work, several kinds of W/IL microemulsions were chosen for DLS analysis because of their applications in the preparation of starch nanoparticles. The compositions of selected microemulsions are as follows: the weight fraction of mixture of TX-100 and 1-butanol in the microemulsions was 0.45, and the mass ratios of [Bmim]PF6 to water (R) are 4:1, 9:1, 15:1, and 20:1, respectively. As shown in Figure 4, the sizes of microemulsions increased from about
■
Figure 2. Phase diagram of the water/TX-100 + 1-butanol/ [Bmim]PF6 (in weight fraction) at 25 °C.
phase region and a one-phase region, could be observed. A continuous stable single-phase microemulsion region could always be observed in the range of the water or [Bmim]PF6 content from 0 to 100% (wt). It could be seen that the phase behavior of the water/TX-100 + 1-butanol/[Bmim]PF6 system was similar to that of the traditional W/O microemulsions and the IL microemulsions reported recently.23 Conductivity. Conductivity is frequently used to investigate the structural changes in microemulsions and can provide a basis for the determination of the cross-linking reaction system.19 The one-phase region could be divided into different subregions, such as the water-in-IL (or oil) microemulsion
Figure 4. Size distribution of the droplets in the water/TX-100 + 1butanol/[Bmim]PF6 microemulsions at 25.0 °C. R represents the mass ratio of [Bmim]PF6 to water. 8216
dx.doi.org/10.1021/jf5018725 | J. Agric. Food Chem. 2014, 62, 8214−8220
Journal of Agricultural and Food Chemistry
Article
of the particles showed aggregation formation mainly due to strong van der Waals force and electrostatic attraction.22 Size Distribution of Starch Nanoparticles. The size distribution of starch nanoparticles was measured using DLS. As observed in Figure 7, the result showed that the size
12.99 to 27.13 nm with the increase of water. The microemulsions showed regular swelling behavior with the addition of water, which demonstrated the formation of W/IL microemulsion according to the study by Pramanik et al.26 FTIR Analysis of Acid-Treated Granular Starch and Starch Nanoparticles. Figure 5 shows the comparative FTIR
Figure 5. FTIR spectra of acid-treated granular starch (a) and starch nanoparticles (b).
spectra of acid-treated granular starch (Figure 5a) and starch nanoparticles (Figure 5b). In the case of acid-treated granular starch, the O−H stretching and the C−H stretching vibration give strong signalsat 3389 and 2928 cm−1, respectively.27 The absorption peak at 1651 cm−1 belonged to O−H bending vibration.28 The bands at 1160, 1084, and 1024 cm−1 were due to C−O stretching vibrations.29 In comparison with acidtreated granular starch, FTIR spectra of starch nanoparticles showed some difference. The absorption peaks at 3389 nd 1651 cm−1 clearly became narrowed and weaker than that of acidtreated granular starch,which demonstrates the occurrence of cross-linking reaction. The band shape between 900 and 1160 cm−1 in starch nanoparticles had changed, and the band intensity became a little stronger compared with acid-treated granular starch. The results suggested that a cross-linking reaction took place between starch molecules. Similar results were also observed in previous literature.4,29 SEM Analysis of Acid-Treated Granular Starch and Starch Nanoparticles. SEM was used to investigate the morphology of acid-treated granular starch and starch nanoparticles. As shown in Figure 6, acid-treated granular starch showed round or oval shapes with various sizes ranging from about 10 to 30 μm. In comparison with the acid-treated granular starch, starch nanoparticles exhibited good sphericity and particle sizes ranged from about 100 to 300 nm, but some
Figure 7. Size distribution of starch nanoparticles.
distribution of starch nanoparticles was relatively concentrated, and the mean diameter was 91.4 nm, which is much smaller than that of starch microspheres prepared by the traditional W/ O emulsion cross-linking method.30 From the result, it could be concluded that starch nanoparticles with a relatively concentrated size distribution could be obtained by using the W/IL microemulsion cross-linking approach. Drug Loading Analysis. According to the scanning result, the testing wavelength of PBS solution containing mitoxantrone hydrochloride was 608 nm. Besides, the standard curve of mitoxantrone hydrochloride absorbance to concentration (from 0.0025 to 0.04 mg/mL) was A = 0.0424 + 24.38C (R2 = 0.9982). The influence of loading time on drug loading property is shown in Figure 8A. The drug loading and encapsulation efficiency increased first and then decreased as time went on. To be exact, the drug loading increased from 0.5102 to 0.7317 mg/g as the time was prolonged from 0.5 to 1.5 h and then decreased to 0.5513 mg/g when the time was extended to 3 h. The encapsulation efficiency increased from 11.54 to 16.55% and then reduced to 12.47% correspondingly. From the result, it could be concluded that the drug loading and encapsulation
Figure 6. SEM images of acid-treated granular starch (a) and starch nanoparticles (b). 8217
dx.doi.org/10.1021/jf5018725 | J. Agric. Food Chem. 2014, 62, 8214−8220
Journal of Agricultural and Food Chemistry
Article
Figure 8. Effect of loading time (A), loading temperature (B), particle size (C), and drug concentration (D) on drug loading property. Other conditions: (A) loading temperature, 17 °C; particle size, 176 nm; drug concentration, 0.0221 mg/mL. (B) loading time, 1.5 h; particle size, 176 nm; drug concentration, 0.0221 mg/mL. (C) loading time, 1.5 h; loading temperature, 17 °C; drug concentration, 0.0221 mg/mL; (D) loading time, 1.5 h; loading temperature, 17 °C; particle size, 64 nm.
efficiency of starch nanoparticles on mitoxantrone hydrochloride presented an appropriate time value. The effect of temperature on drug loading property is observed in Figure 8B. It was obvious that different loading temperatures resulted in significant changes in drug loading and encapsulation efficiency. At a temperature of 17 °C, starch nanoparticles loaded with more mitoxantrone hydrochloride, and encapsulation efficiency showed the same trend. The reason for this phenomenon may be that the adsorption of mitoxantrone hydrochloride was mainly attributed to the existence of opposite charges and high affinity. This adsorption process would be hindered by high temperature; thus, the drug loading reduced at higher temperature.15 Starch nanoparticles with different particle sizes (64, 176, and 255 nm) were obtained through changing the reaction conditions such as reaction time, reaction temperature, and starch concentration to investigate the effect of particle size on drug loading property. As shown in Figure 8C, drug loading and encapsulation efficiency decreased with increasing particle size of starch nanoparticles. The reason for this phenomenon may be that starch nanoparticles of smaller particle size have greater specific surface area and stronger adhesion ability. As shown in Figure 8D, drug loading ascended significantly from 0.7317 to 1.5587 mg/g as the concentration of mitoxantrone hydrochloride rose from 0.0221 to 0.1326 mg/ mL. However, the increase of drug concentration caused a decline in encapsulation efficiency. Therefore, higher drug concentration does not necessarily result in better drug loading property. Drug Release Analysis. Drug release experiments were performed in PBS solution. As presented in Figure 9, an initial burst release was observed in the first hour after the drug-
Figure 9. Mitoxantrone hydrochloride release of starch nanoparticles in PBS solution.
loaded starch nanoparticles were immersed into release medium. The high release rate of 32.15% in the first hour was associated with the immediate dispersion of the mitoxantrone hydrochloride close to the surfaces of starch nanoparticles. In the following 9 h, the starch nanoparticles presented a swelling-controlled and sustained release, in which the release rate tailed off, and 79.95% of mitoxantrone hydrochloride contained in the starch nanoparticles was released in the 10th hour. This may be explained by increasing swelling causing a great number of mitoxantrone hydrochloride molecules to diffuse out of the starch nanoparticles and pass into the release medium. This observed phenomenon was consistent with the results of Fang et al.15 This paper describes an exploratory study on the preparation of starch nanoparticles by a novel ionic liquid microemulsion 8218
dx.doi.org/10.1021/jf5018725 | J. Agric. Food Chem. 2014, 62, 8214−8220
Journal of Agricultural and Food Chemistry
Article
media dependent responsive behavior to be used as drug delivery carriers. J. Mater. Sci. Mater. Med. 2006, 17, 371−377. (7) Mao, S. R.; Chen, Z. M.; Wei, Z. P.; Liu, H.; Bi, D. Z. Intranasal administration of melatonin starch microspheres. Int. J. Pharm. 2004, 272, 37−43. (8) Bjork, E.; Edman, P. Characterization of degradable starch microspheres as a nasal delivery system for drugs. Int. J. Pharm. 1990, 62, 187−192. (9) Hamdi, G.; Ponchel, G. Enzymatic degradation of epichlorohydrin crosslinked starch microspheres by α-amylase. Pharm. Res. 1999, 16, 867−875. (10) Gyves, J. W.; Ensminger, W. D.; VanHarken, D.; Niederhuber, J.; Stetson, P.; Walker, S. Improved regional selectivity of hepatic arterial mitomycin by starch microspheres. Clin. Pharmacol. Ther. 1983, 34, 259−265. (11) Ishida, K.; Hirooka, M.; Hiraoka, A.; Kumagi, T.; Uehara, T.; Hiasa, Y. Treatment of hepatocellular carcinoma using arterial chemoembolization with degradable starch microspheres and continuous arterial infusion of 5-fluorouracil. Jpn. J. Clin. Onol. 2008, 38, 596−603. (12) Kim, D. K.; Mikhaylova, M.; Wang, F. H.; Kehr, J.; Bjelke, B.; Zhang, Y. Starch-coated superparamagnetic nanoparticles as MR contrast agents. Chem. Mater. 2003, 1, 4343−4351. (13) Franssen, O.; Hennink, W. E. A novel preparation method for polymeric microparticles without the use of organic solvents. Int. J. Pharm. 1998, 168, 1−7. (14) Shi, A. M.; Li, D.; Wang, L. J.; Li, B. Z.; Adhikaric, B. Preparation of starch-based nanoparticles through high-pressure homogenization and miniemulsion cross-linking: influence of various process parameters on particle size and stability. Carbohydr. Polym. 2011, 83, 1604−1610. (15) Fang, Y. Y.; Wang, L. J.; Li, D.; Li, B. Z.; Bhandari, B.; Chen, X. D.; Mao, Z. H. Preparation of crosslinked starch microspheres and their drug loading and releasing properties. Carbohydr. Polym. 2008, 74, 379−384. (16) Welton, T. Room-temperature ionic liquids: solvents for synthesis and catalysis. Chem. Rev. 1999, 99, 2071−2083. (17) Cheng, S. Q.; Fu, X. G.; Liu, J. H.; Zhang, J. L.; Zhang, Z. F.; Wei, Y. L. Study of ethylene glycol/TX-100/ionic liquid microemulsions. Colloids Surf., A 2007, 302, 211−215. (18) Cheng, S. Q.; Han, F.; Wang, Y. R.; Yan, J. F. Effect of cosurfactant on ionic liquid solubilization capacity in cyclohexane/TX100/1-butyl-3-methylimidazolium tetrafluoroborate microemulsions. Colloids Surf., A 2008, 317, 457−461. (19) Gao, H. X.; Li, J. C.; Han, B. X.; Chen, W. N.; Zhang, J. L.; Zhang, R.; Yan, Y. D. Microemulsions with ionic liquid polar domains. Phys. Chem. Chem. Phys. 2004, 6, 2914−2916. (20) Yan, F.; Texter, J. Surfactant ionic liquid-based microemulsions for polymerization. Chem. Commun. 2006, 25, 2696−2698. (21) Zhang, G. P.; Kuang, Y. F.; An, C. L.; Liu, D.; Huang, Z. Y.; Kuang, Y. F. Bimetallic palladium-gold nanoparticles synthesized in ionic liquid microemulsion. Colloid Polym. Sci. 2012, 290, 1435−1441. (22) Zhou, G.; Luo, Z. G.; Fu, X. Preparation and characterization of starch nanoparticles in ionic liquid-in-oil microemulsions system. Ind. Crops Prod. 2014, 52, 105−110. (23) Najjar, R.; Stubenrauch, C. Phase diagrams of microemulsions containing reducing agents and metal salts as bases for the synthesis of metallic nanoparticles. J. Colloid Interface Sci. 2009, 331, 214−220. (24) Gao, Y.; Han, S.; Han, B.; Li, G.; Shen, D.; Li, Z.; Du, J.; Hou, W.; Zhang, G. TX-100/water/1-butyl-3-methylimidazolium 322 hexafluorophosphate microemulsions. Langmuir 2005, 21, 5681−5684. (25) Cheng, S. Q.; Fu, X. G.; Liu, J. H.; Zhang, J. L.; Zhang, Z. F.; Wei, Y. L. Study of ethylene glycol/TX-100/ionic liquid microemulsions. Colloids Surf., A 2007, 302, 211−215. (26) Pramanik, R.; Ghatak, C.; Rao, V. G.; Sarkar, S.; Sarkar, N. J. Room temperature ionic liquid in confined media: a temperature dependence solvation study in [bmim][BF4]/BHDC/benzene reverse micelles. J. Phys. Chem. B 2011, 115, 5971−5979.
and drug loading and releasing properties of starch nanoparticles. Water/TX-100 + 1-butanol/[Bmim]PF6 microemulsions were prepared, and the pseudoternary phase diagram was drawn to investigate the phase behavior. The W/IL, bicontinuous, and IL/W microregions of the microemulsions were identified by conductivity measurements. DLS analysis of microemulsions demonstrated the formation of a W/IL microemulsion. Cross-linked starch nanoparticles were prepared with epichlorohydrin as cross-linker through a W/IL microemulsion cross-linking approach. The formation of crosslinking bonds in starch molecules was demonstrated by FTIR spectra. SEM and DLS of starch nanoparticles intuitively suggested the formation of starch nanoparticles. In terms of drug loading property of starch nanoparticles, it was found that the drug loading and encapsulation efficiency were influenced by loading time, loading temperature, and particle size as well as drug concentration. The release curve of drug-loaded starch nanoparticles contained two phases: an initial burst release phase and a sustained release phase depending on the swelling and degradation of starch nanoparticles.
■
AUTHOR INFORMATION
Corresponding Authors
*(Z.L.) Phone: +86-20-87113845. Fax: +86-20-87113848. Email:
[email protected]. *(X.F.) Phone: +86-20-87113845. E-mail:
[email protected]. Funding
This research was supported by the National Natural Science Foundation of China (21376097, 21004023), the program for New Century Excellent Talents in University (NCET-130212), the Guangdong Natural Science Foundation (S2013010012318), the Key Project of Science and Technolo g y o f G ua n g d o n g P r o v i n c e ( 2 0 1 2 B 0 9 1 1 00 4 4 3 , 2012B091100047), and the Fundamental Research Funds for the Central Universities, SCUT (2013ZZ0070). Notes
The authors declare no competing financial interest.
■
ABBREVIATIONS USED W/IL, water-in-ionic liquid; TX-100, Triton X-100; [Bmim]PF6, 1-butyl-3-methylimidazolium hexafluorophosphate; DLS, dynamic light scattering; FTIR, Fourier transform infrared spectroscopy; SEM, scanning electron microscopy; IL/W, ionic liquid-in-water; W/O, water-in-oil; ILs, ionic liquids
■
REFERENCES
(1) Jobling, S. Improving starch for food and industrial applications. Curr. Opin. Plant Biol. 2004, 7, 210−218. (2) Raina, C. S.; Singh, S.; Bawa, A. S.; Saxena, D. C. A comparative study of Indian rice starches using different modification model solutions. Food Sci. Technol. 2007, 40, 885−892. (3) Kim, M.; Lee, S. J. Characteristics of crosslinked potato starch and starch-filled linear low-density polyethylene films. Carbohydr. Polym. 2002, 50, 331−337. (4) Mundargi, R. C.; Shelke, N. B.; Rokhade, A. P.; Patil, S. A.; Aminabhavi, T. M. Formulation and in-vitro evaluation of novel starch-based tableted microspheres for controlled release of ampicillin. Carbohydr. Polym. 2007, 71, 42−53. (5) Stertman, L.; Lundgren, E.; Sjöholm, I. Starch microparticles as a vaccine adjuvant: only uptake in Peyer’s patches decides the profile of the immune response. Vaccine 2006, 24, 3661−3668. (6) Malafaya, P. B.; Stappers, F.; Reis, R. L. Starch-based microspheres produced by emulsion crosslinking with a potential 8219
dx.doi.org/10.1021/jf5018725 | J. Agric. Food Chem. 2014, 62, 8214−8220
Journal of Agricultural and Food Chemistry
Article
(27) Kacurakova, M.; Wilson, R. H. Developments in mid-infrared FTIR spectroscopy of selected carbohydrates. Carbohydr. Polym. 2001, 44, 291−303. (28) Mano, J. F.; Koniarova, D.; Reis, R. L. Thermal properties of thermoplastic starch/synthetic polymer blends with potential biomedical applicability. J. Mater. Sci. Mater. Med. 2003, 14, 127−135. (29) Li, B. Z.; Wang, L. J.; Li, D.; Adhikari, B.; Mao, Z. H. Preparation and characterization of crosslinked starch microspheres using a two-stage water-in-water emulsion method. Carbohydr. Polym. 2012, 88, 912−916. (30) Zhao, X. F.; Li, Z. J.; Wang, L.; Lai, X. J. Synthesis, characterization, and adsorption capacity of crosslinked starch microspheres with N,N′-methylene bisacrylamide. J. Appl. Polym. Sci. 2008, 109, 2571−2575.
8220
dx.doi.org/10.1021/jf5018725 | J. Agric. Food Chem. 2014, 62, 8214−8220
