Preparation and in vitro evaluation of new pH‐sensitive hydrogel beads for oral delivery of protein drugs

New biodegradable pH‐responsive hydrogel beads based on chemically modified chitosan and sodium alginate were prepared and characterized for the controlled release study of protein drugs in the small intestine. The ionotropic gelation reaction was carried out under mild aqueous conditions, which should be appropriate for the retention of the biological activity of an uploaded protein drug. The equilibrium swelling studies were carried out for the hydrogel beads at 37°C in simulated gastric (SGF) and simulated intestinal (SIF) fluids. Bovine serum albumin (BSA), a model for protein drugs was entrapped in the hydrogels and the in vitro drug release profiles were established at 37°C in SGF and SIF. The preliminary investigation of the hydrogel beads prepared in this study showed high entrapment efficiency (up to 97%) and promising release profiles of BSA. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis,characterization, and drug‐release behavior of amphiphilic quaternary ammonium chitosan derivatives

A new type of amphiphilic quaternary ammonium chitosan derivative, 2‐N‐carboxymethyl‐6‐O‐diethylaminoethyl chitosan (DEAE–CMC), was synthesized through a two‐step Schiff base reaction process and applied to drug delivery. In the first step, benzaldehyde was used as a protective agent for the incorporation of diethylaminoethyl groups to form the intermediate (6‐O‐diethylaminoethyl chitosan). On the other hand, NaBH₄ was used as a reducing agent to reduce the Schiff base, which was generated by glyoxylic acid, for the further incorporation of carboxymethyl groups to produce DEAE–CMC. The structure, thermal properties, surface morphology, and diameter distribution of the resulting chitosan graft copolymers were characterized by Fourier transform infrared spectroscopy, ¹H‐NMR, thermogravimetric analysis, differential scanning calorimetry, X‐ray powder diffraction, scanning electron microscopy, and laser particle size analysis. Benefiting from the amphiphilic structure, DEAE–CMC was able to be formed into microspheres in aqueous solution with an average diameter of 4.52 ± 1.21 μm. An in vitro evaluation of these microspheres demonstrated their efficient controlled release behavior of a drug. The accumulated release ratio of vitamin B₁₂ loaded DEAE–CMC microspheres were up to 93%, and the duration was up to 15 h. The grafted polymers of DEAE–CMC were found to be blood‐compatible, and no cytotoxic effect was shown in human SiHa cells in an MTT [3‐(4, 5‐dimethyl‐thiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide] cytotoxicity assay. These results indicate that the DEAE–CMC microspheres could be used as safe, promising drug‐delivery systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39890.     

Preparation of surface‐modified,micrometer‐sized carboxymethyl chitosan drug‐loaded microspheres

Drug‐loaded microspheres have attracted much attention in embolization therapy for liver cancer in recent years. Carboxymethyl chitosan has obvious advantages for biomedical applications because of its exceptional biocompatibility and biodegradability. In this study, surface‐modified carboxymethyl chitosan microspheres were prepared by the crosslinking reactions of carboxymethyl chitosan in a reverse suspension system with poly(ethylene glycol diglycidyl ether) (PEGDE) as the crosslinking agent; this was followed by the grafting polymerization of 2‐acrylamido‐2‐methyl propane sulfonic acid on the surface of the microspheres. The microspheres showed regular spherical shapes with size distributions ranging from 300 to 600 μm. Ion‐exchange groups (? COOH, ? SO₃H) were introduced into the microspheres; these groups could load doxorubicin with a loading rate as high as 34.6% in 24 h. This was an increase of 49.8% compared to that of the pure carboxymethyl chitosan microspheres. Additionally, the microspheres possessed large network structures because macromolecular PEGDE was used as the crosslinking agent. The drug‐release profile showed that the surface‐modified microspheres displayed a sustained‐release manner compared with the nonmodified microspheres in phosphate‐buffered saline. These microspheres have promising applications as drug‐loaded arterial embolization agents for the interventional treatment of tumors. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45731.     

Preparation and release behavior of carboxymethylated chitosan/alginate microspheres encapsulating bovine serum albumin

Microspheres were prepared from carboxymethylated chitosan (CM‐chitosan) and alginate by emulsion phase separation. Their structure and morphology were characterized with IR spectroscopy and scanning electron microscopy. Bovine serum albumin (BSA) was encapsulated in the microspheres to test the release behavior. The swelling behavior, encapsulation efficiency, and release behavior of BSA from the microspheres at different pHs and with a pH‐gradient condition were investigated. The BSA encapsulation efficiency was calculated to be 80%. The degree of swelling of the microspheres without BSA loaded at pH 7.2 was much higher than that at pH 1.0. The encapsulated BSA was quickly released in a Tris–HCl buffer (pH 7.2), whereas a small amount of BSA was released under acid conditions (pH 1.0) because of the strong electrostatic interaction between ? NH₂ groups of CM‐chitosan and ? COOH groups of alginic acid and a dense structure caused by a Ca²⁺ crosslinked bridge. For the simulation of the processing of the drug under the conditions of the intestine, the microspheres were tested in a pH‐gradient medium, in which an acceleration of the release occurred at pH 7.4 after a lag time at a low pH (5.8–6.8). At pH 7.4, a large amount of BSA was released from the microspheres in a short time because of the rapid swelling of the microspheres. However, the release only depended on the diffusion of BSA at relatively low pHs, this resulted in a relatively low release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 878–882, 2004     

Characterization of novel quaternary chitosan derivative nanoparticles loaded with protein

The objective of this work was to characterize a novel quaternary chitosan derivative [O‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (O‐HTCC)] nanoparticle system. O‐HTCC nanoparticles were prepared with a simple and mild ionic gelation method upon the addition of a sodium tripolyphosphate solution to a low‐molecular‐weight O‐HTCC solution. Highly cationic chitosan nanoparticles were prepared. Bovine serum albumin (BSA), a model protein drug, was incorporated into the nanoparticles. The physicochemical properties of the nanoparticles were determined with transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared analysis, differential scanning calorimetry, and X‐ray diffraction (XRD) patterns. The results showed that increasing the BSA concentration from 1.5 to 2.5 mg/mL promoted the BSA encapsulation efficiency from 57.3% to 87.5% and the loading capacity from 70.2% to 99.5%. Compared with the chitosan nanoparticles, the O‐HTCC nanoparticles had lower burst release. TEM revealed that the BSA‐loaded O‐HTCC nanoparticles were smaller than the O‐HTCC nanoparticles when the BSA concentration was 1.5 mg/mL; SEM showed that the size of the BSA‐loaded O‐HTCC nanoparticles was mostly affected by the BSA concentration, and the increase in size occurred with the concentration increasing. Thermograms and XRD of the BSA‐loaded nanoparticles suggested that polyelectrolyte–protein interactions increased with the BSA concentration increasing and greater chain realignment in the BSA‐loaded nanoparticles. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermo‐ and pH‐responsive behaviors of graft copolymer and blend based on chitosan and N‐isopropylacrylamide

Thermo‐ and pH‐sensitive polymers were prepared by graft polymerization or blending of chitosan and poly(N‐isopropylacrylamide) (PNIPAAm). The graft copolymer and blend were characterized by Fourier transform‐infrared, thermogravimetric analysis, X‐ray diffraction measurements, and solubility test. The maximum grafting (%) of chitosan‐g‐(N‐isopropylacrylamide) (NIPAAm) was obtained at the 0.5 M NIPAAm monomer concentration, 2 × 10⁻³ M of ceric ammonium nitrate initiator and 2 h of reaction time at 25°C. The percentage of grafting (%) and the efficiency of grafting (%) gradually increased with the concentration of NIPAAm up to 0.5 M, and then decreased at above 0.5 M NIPAAm concentration due to the increase in the homopolymerization of NIPAAm. Both crosslinked chitosan‐g‐NIPAAm and chitosan/PNIPAAm blend reached an equilibrium state within 30 min. The equilibrium water content of all IPN samples dropped sharply at pH > 6 and temperature > 30°C. In the buffer solutions of various pH and temperature, the chitosan/PNIPAAm blend IPN has a somewhat higher swelling than that of the chitosan‐g‐NIPAAm IPN. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 1381–1391, 2000     

Investigation of adsorption–desorption dynamism of bovine serum albumin on crosslinked N,N′‐diethylaminoethyl dextran microbeads: Solution phase

New hydrogel microspheres based on crosslinked dextran containing N,N′‐diethylaminoethyl (DEAE) groups with different chemical structures have been used in adsorption–desorption studies. Bovine serum albumin (BSA) is frequently used in biophysical and biochemical studies. BSA has a well‐known primary structure that has been associated with binding of many different categories of small molecules. Both adsorption kinetics and equilibrium isotherms for the adsorption of BSA on crosslinked DEAE dextran have been determined experimentally. These were only slightly dependent on the initial concentration of BSA but were considerably affected by the pH of the medium. The results fitted the Freundlich–Langmuir isotherm model for pH 6.9. The adsorption capacity factor and the adsorption equilibrium constant were obtained and mathematical modeling of adsorption, adsorption rate constants, and maximum adsorption were determined. Swelling kinetics of crosslinked DEAE dextran and optimum ionic strength, pH, and mass of hydrogel were also investigated. Desorption studies were finally determined under optimum medium conditions. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Release of indomethacin from a novel chitosan microsphere prepared by a naturally occurring crosslinker: Examination of crosslinking and polycation–anionic drug interaction

Novel chitosan microspheres with lower cytotoxicity were fabricated in this study and their drug release characteristics were investigated. Genipin, a naturally occurring crosslinking reagent that has been used in herbal medicine and in the production of food dye, was used to prepare crosslinked chitosan microspheres by a water‐in‐oil dispersion method. The crosslinking mechanism examined by FTIR and ¹³C–NMR suggests that the crosslinking of chitosan by genipin leads to the formation of secondary amide and heterocyclic amino linkage. The polycation–anionic drug interaction between chitosan and indomethacin was pH dependent and could affect the dissolution property of indomethacin. By examination of the release profiles of the crosslinked chitosan microsphere, it was found that the release of indomethacin from the microsphere was sustainable and influenced by factors such as crosslinking of microsphere and chitosan–indomethacin interaction, thus establishing crosslinked chitosan microsphere as a very promising polymeric carrier for drug release. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1700–1711, 2001     

Preparation and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles

Dexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of ?2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41199.     

Prolonged zero‐order BSA release from pH‐sensitive hydrogels of poly(AAc‐co‐DMAPMA) having rich nano through micro scale morphology

New variety of pH‐sensitive hydrogels, having macroporous interior with honey‐comb type architecture and continuous skin at the surface, have been developed by single step aqueous copolymerization of acrylic acid (AAc) and N‐[3‐(dimethylamino)propyl]‐methacrylamide (DMAPMA) in different feed ratios at 41 ± 1°C. Interlocked nanogels of ～ 300 nm were identified as the building blocks in all of these cylindrical poly(AAc‐co‐DMAPMA) matrices (PDMAAc). The gels showed good compressive strength even at a swelling as high as 4330% (mass) at pH 7.0. Morphology of McCoy fibroblast cell line remained unchanged in direct contact with different PDMAAc gels, and cell viability (±SD) was recorded to be in the range of 105 (±3)% to 87 (±8)% after 72 h. Bovine serum albumin (BSA) loaded gels were prepared by means of equilibrium partitioning. Loading efficiency of PDMAAc gels has been found to be in the range of 210–277 mg/g dry gel. BSA release from PDMAAc gels at 37°C has been found to follow non‐Fickian diffusion mechanism in simulated gastric juice (pH 1.2), and Case II transport in simulated intestinal juice (pH 7.4). In vitro study showed that the gels are capable of retaining >95% of the loaded BSA in gastric medium through average gastric emptying period. Again, ～ 56% BSA release was recorded in 24 h at pH 7.4, indicating prolonged BSA diffusion in intestinal condition. Constant rate of BSA diffusion was reflected from the release profiles at both the pH. Diffusion exponents also supported the same and indicated for absolute zero‐order kinetics at pH 7.4. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Characterization of ketoprofen‐loaded PEG‐CH semi‐IPN system for wound dressing application

Polymer systems, in the form of crosslinking networks, have been widely used in biomedicine. However, they are a challenge mainly due to the impact of their physicochemical properties on release kinetics of drugs. Ketoprofen is an analgesic anti‐inflammatory drug with short half‐life (<2 h) and quickly eliminated by the body. Topical administration of ketoprofen can reduce pain, accelerate the wound healing process, and minimize the risk of systemic side effects. Therefore, the aim was to synthesize, characterize, and evaluate a novel ketoprofen polymer system in the form of a semi‐interpenetrated network of poly(ethylene glycol)‐chitosan. The pore size studied by small‐angle X‐ray scattering showed the presence of nanoscale pores, 13.7 nm (dry state) and 26.18 nm (swollen form). The maximum swelling was 420 ± 45% at 24 h. Finally, the encapsulated ketoprofen (6.5%) was released at a constant concentration (0.12 ± 0.03 mg/mL, 8 h) and half of the doses up to 24 h. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46644.     

Development of fibrin conjugated chitosan/nano β‐TCP composite scaffolds with improved cell supportive property for bone tissue regeneration

In the present study, an attempt has been made to improve cell supportive property of chitosan/nano beta tri‐calcium phosphate (β‐TCP) composite scaffolds by modification of scaffold surface with fibrin using ethyl‐3‐(3‐dimethylaminopropyl) carbodimide (EDC) as crosslinking agent. The developed fibrin conjugated chitosan/nano β‐TCP composite scaffolds possess desired pore size and porosity in the range of 45–151 µm and 81.4 ± 4.1%, respectively. No significant change in compressive strength of scaffolds was observed before and after fibrin conjugation. The calculated compressive strength of fibrin conjugated and non‐conjugated chitosan/nano β‐TCP scaffolds are 2.71 ± 0.14 MPa and 2.67 ± 0.11 MPa, respectively. Results of cell culture study have further shown an enhanced cell attachment, cell number, proliferation, differentiation, and mineralization on fibrin conjugated chitosan/nano β‐TCP scaffold. The uniform cell distribution over the scaffold surface and cell infiltration into the scaffold pores were assessed by confocal laser scanning microscopy. Furthermore, higher expression of osteogenic specific genes such as bone sialo protein, osteonectin, alkaline phosphatase, and osteocalcin (OC) on fibrin conjugated scaffolds was observed when compared to scaffolds without fibrin. Altogether, results indicate the potentiality of developed fibrin conjugated composite scaffolds for bone tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41534.     

Preparation of polyamidoamine dendrons supported on chitosan microspheres and the adsorption of bilirubin

The aim of this study was to prepare a new adsorbent for bilirubin (BR); low generation (G, G ≤4) hexanediamine‐containing polyamidoamine (PAMAM) dendrons were supported on chitosan (CS) microspheres (CS‐Gn, n = 0,1,2,3,4). The adsorption properties of this novel adsorbent for BR in aqueous solution were examined. The adsorption percentages were over 70% at 0.5 h and over 90% at 1 h. The adsorption capacity was up to 43 mg/g and was not yet saturated. The BR adsorption increased with increasing temperature and increasing BR initial concentration and was the highest at pH 7.4; it decreased slightly with increasing ionic strength and occurred even in the presence of bovine serum albumin (BSA). We observed that the CS–Gn microspheres had satisfactory competitive abilities with BSA, although the adsorption percentage decreased a certain extent in the presence of BSA. In addition, the CS–Gn microspheres were easier to prepare than the usual PAMAM dendrimers. In summary, this adsorbent is a promising biomedical material for BR removal for artificial liver supported systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Properties of chitosan/poly(vinyl alcohol) films for drug‐controlled release

With bovine serum albumin (BSA) as a model drug, drug‐loaded films of chitosan (CS) and poly(vinyl alcohol) (PVA) were obtained by a casting/solvent evaporation method and crosslinked by tripolyphosphate (TPP). The films were characterized by FTIR, XRD, and SEM. The influential factors of drug‐loaded films on drug‐controlled release were studied. These factors included, primarily, the component ratio of CS and PVA, the loaded amount of BSA, the pH and ionic strength of the release solution, and the crosslinking time with TPP. The results showed that within 25 h, when the weight ratios of CS to PVA in the drug‐loaded films were 90 : 10, 70 : 30, 50 : 50, and 30 : 50, the cumulative release rates of BSA were 63.3, 72.9, 81.8, and 91.8%, respectively; when the amounts of model drug were 0.1, 0.2, and 0.3 g, the release rates were 100, 81.8, and 59.6%, respectively; when the pH values of the drug release medium were 1.0, 3.8, 5.4, and 7.4, the release rates reached 100, 100, 37.9, and 7.8%, respectively; the cumulative release rates of BSA were 78.4, 82.3, 84.3, and 91.7% when the ionic strengths of the release solution were, respectively, 0.1, 0.2, 0.3, and 0.4M; when the crosslinking times of these drug films in the TPP solution were 0, 5, 15, 30, and 60 min, the release rates attained 100, 100, 81.8, 65, and 43.3%, respectively. All the results indicated that the CS/PVA film was useful in drug delivery systems. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 808–813, 2005     

Chitosan and chitosan/β‐cyclodextrin microspheres as sustained‐release drug carriers

The main aim of this study was to compare two microspheres, chitosan (CTS) and CTS/β‐cyclodextrin (β‐CD), made by spray‐drying, as pulmonary sustained drug‐delivery carriers. Theophylline (TH) was used as a model drug. The characteristics of the microspheres and in vitro release were studied. The yield of CTS/β‐CD microspheres was 46.1%, which was higher than that of the CTS microspheres (36.5%). The drug loads of the CTS and CTS/β‐CD microspheres were 22.7 and 21.1%, respectively, whereas the encapsulation efficiencies were 90.7 and 91.4%, respectively. The distribution of 50% [(diameter) d (0.5)] of the CTS microspheres was below 6.49 μm and that of the CTS/β‐CD microspheres was below 4.90 μm. Scanning electron microscopy showed that both microspheres yielded a spherical shape with smooth or wrinkled surfaces. Fourier transform infrared spectroscopy demonstrated that the carbonyl group of TH formed hydrogen bonds with the amide group of CTS and the hydroxyl group of β‐CD. The swelling ability of the two microspheres was more than three times their weight, and their humidity rates attained equilibrium within 24 h. The ciliary beat movement times of CTS and CTS/β‐CD microspheres were 493.00 and 512.33 min, respectively, which indicated that the two microspheres effectively reduced the ciliotoxicity and possessed better adaptability. In vitro release of TH from CTS/β‐CD microspheres was slower than that from CTS microspheres at pH 6.8 and provided a sustained release of 72.0% within 12 h. The results suggest that CTS/β‐CD microspheres are a promising carrier for sustained release for pulmonary delivery. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1183–1190, 2007     

PEGylated chitosan microspheres as mucoadhesive drug‐delivery carriers for puerarin

PEGylated chitosans with different degrees of grafting were synthesized, and the application potential of microspheres based on PEGylated chitosan as mucoadhesive drug‐delivery carriers for puerarin was investigated. Compared with chitosan microspheres, PEGylated chitosan microspheres (PCMs) exhibited better physical stability and higher swelling capacity, and the amount of water uptake increased as the content of poly(ethylene glycol) methyl ether in the microspheres increased. PCMs showed obviously improved mucoadhesive behavior on a mucosa‐like surface. Puerarin was incorporated into the microspheres, and the release experiments in vitro showed that the PEGylation of chitosan accelerated puerarin release from the particles and decreased the retention of the drug. The abilities of all of the tested microspheres to open tight junctions and improve the permeability of puerarin were demonstrated with a Caco‐2 cell monolayer as an in vitro model. The amount of puerarin permeating across the Caco‐2 cell monolayer was significantly increased by the incorporation of puerarin into the PCMs. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42623.     

Preparation of O‐hydroxypropyl‐N‐butyl chitosan under microwave irradiation

O‐Hydroxypropyl‐N‐butyl chitosan (C₄‐HPCS) was prepared by microwave irradiation and phase‐transfer catalysis; this consisted of two steps: (1) the synthesis of O‐hydroxypropyl chitosan (HPCS) with chitosan and propylene oxide and (2) the synthesis of C₄‐HPCS with HPCS and 1‐butyl bromide. The results of the experiment are as follows: Fourier transform infrared spectroscopy and ¹H‐NMR displayed the characteristic peaks of C₄‐HPCS, thermogravimetric analysis showed that C₄‐HPCS was stable until 240°C, the critical micelle concentration was 0.025 wt %, the surface tension was equal to 65.70 ± 0.09 mN/m, the hydrophile–lipophile balance number value was 13.55, and the emulsifying power, foaming expansion, and foaming volume stability were 73.10, 45, and 94 wt %, respectively. This indicated that C₄‐HPCS had superior surface performance and more excellent hydrophilicity. In addition, the microwave irradiation and phase‐transfer catalysis used in the experiment were considered to be more environmentally friendly and time‐saving methods. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41527.     

Synthesis of monodisperse crosslinked poly(styrene‐co‐divinylbenzene) microspheres by precipitation polymerization in acetic acid

Poly(styrene‐co‐divinylbenzene) microspheres with size ranging from 1.6 to 1.8 μm were prepared in acetic acid by precipitation polymerization. The particle size and particle size distribution were determined by laser diffraction particle size analyzer, and the morphology of the particles was observed with scanning electron microscope. Besides, effects of various polymerization parameters such as initiator and total monomer concentration, divinylbenzene (DVB) content, polymerization time and polymerization temperature on the morphology and particle size were investigated in this article. In addition, the yield of microspheres increased with the increasing total monomer concentration, initiator loading, DVB concentration and polymerization time. In addition, the optimum polymerization conditions for synthesis of monodisperse crosslinked poly(styrene‐co‐divinylbenzene) microspheres by precipitation polymerization in acetic acid were obtained. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Reinforcing biopolymer hydrogels with ionic‐covalent entanglement hydrogel microspheres

Microscopic hydrogel spheres can be used to improve the mechanical properties of conventional hydrogels. We prepared ionic‐covalent entanglement (ICE) hydrogel microspheres of calcium cross‐linked gellan gum and genipin cross‐linked gelatin using a water‐in‐oil emulsion‐based processing technique. The method was optimized to produce microspheres with number average diameter 4 ± 1 µm. These ICE microspheres were used to reinforce gelatin hydrogels and improve their compressive mechanical properties. The strongest microsphere reinforced hydrogels possessed a compressive mechanical stress at failure of 0.50 ± 0.1 MPa and a compressive secant modulus of 0.18 ± 0.02 MPa. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40557.