Poly(HEMA)/cyclodextrin‐based hydrogels for subconjunctival delivery of cyclosporin A

To enhance the solubility and ocular permeability of immunosuppressive agent, cyclosporine A (CsA), three types of delivery systems were prepared using (2‐hydroxypropyl)‐β‐cyclodextrin (HPβCD), and 2‐hydroxyethyl methacrylate (HEMA). Those systems are (i) hydrogels of HPβCD with crosslinking agent ethylene glycol diglycidylether, (ii) poly(HEMA) hydrogels, and (iii) different amounts of HPβCD‐containing poly(HEMA) hydrogels indicated as poly(HEMA‐co‐HPβCD). In the presence of HEMA, hydrogels have desired mechanical integrity with lower equilibrium content than that of hydrogels without HEMA. CsA was loaded into the HPβCD‐based hydrogels by embedding from its aqueous suspensions in higher amounts than that of the poly(HEMA) hydrogels that were loaded by CsA–HPβCD complex solution. Although the poly(HEMA) hydrogels are releasing total CsA in 3 days, long‐term release was realized from HPβCD‐based hydrogels. For subconjunctival administration, regarding to the amounts of loaded CsA, release profiles, and mechanical integrity, the most suitable system is poly(HEMA‐co‐HPβCD) hydrogels in high HPβCD content. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40397.     

Synthesis,characterization and application of poly[(1‐vinyl‐2‐pyrrolidone)‐co‐(2‐hydroxyethyl methacrylate)] as controlled‐release polymeric system for 2,4‐dichlorophenoxyacetic chloride using an ultrafiltration technique

BACKGROUND: Polymers supporting chemicals used in agriculture have recently been developed to overcome the serious environmental problems of conventional agrochemicals. The success of these formulations is based on a suitable choice of polymer support. Degradable polymeric hydrogels are of particular interest. The gradual release of the bioactive agent can be achieved by hydrolytic or enzymatic cleavage of the linking bond. RESULTS: In this context, poly[(1‐vinyl‐2‐pyrrolidone)‐co‐(2‐hydroxyethyl methacrylate)] [poly(NVP‐co‐HEMA)] has been used as a bioactive carrier reagent. Herein, we report a controlled‐release system with the herbicide 2,4‐dichlorophenoxyacetic acid (2,4‐D) using an ultrafiltration system. Hydrolysis was studied by testing the release at various pH values. A high release with poly(NVP‐co‐HEMA)–2,4‐D was observed at pH = 7 and 10 after two days (Z = 2). The release percentage of copolymer–herbicide increased at pH = 10. It showed release values between 79.0 and 94.5%. Poly(NVP‐co‐HEMA)–herbicide can release a bioactive compound in aqueous solution at pH = 3, 7 and 10. CONCLUSION: Based on the results of homogeneous hydrolysis, it is argued that the herbicide release rate depends on the pH of the reaction environment. This functional polymer could be employed as a biodegradable material for applications in agrichemical release. Copyright © 2008 Society of Chemical Industry     

Synthesis and characterization of a porous poly(hydroxyethylmethacrylate‐co‐ethylene glycol dimethacrylate)‐based hydrogel device for the implantable delivery of insulin

Poly(hydroxyethylmethacrylate‐co‐ethylene glycol dimethacrylate) [poly(HEMA‐co‐EGDMA)]‐based hydrogel devices were synthesized by a free‐radical polymerization reaction with 2‐hydroxyethylmethacrylate as the monomer, different concentrations of ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and ammonium persulfate/N,N,N′,N′‐tetra‐methyl ethylenediamine as the free‐radical initiator. The porosity of the poly(HEMA‐co‐EGDMA) hydrogels was controlled with water as the porogen. The Fourier transform infrared spectrum of poly(HEMA‐co‐EGDMA) showed absorption bands associated with ? C?O stretching at 1714 cm^?1, C? O? C stretching vibrations at 1152 cm^?1, and a broad band at 3500–3800 cm^?1 corresponding to ? OH stretching. Atomic force microscopy studies showed that the hydrogel containing 67% water had pores in the range of 3500–9000 nm, whereas the hydrogel containing 7% water did not show measurable pores. The hydrogel synthesized with 1% EGDMA showed 50% thallium‐201 release within the first 30 min and about 80% release within 60 min. In vitro insulin‐release studies suggested that the hydrogel with 27% water showed sustained release up to 120 min, whereas the hydrogels with 47 and 67% water showed that nearly all of the insulin was released within 60 min. Hydrogel devices synthesized with 27% water and filled with insulin particles showed sustained release for up to 8 days, whereas the hydrogels synthesized with 47 and 67% water released insulin completely within 3 days of administration. Animal studies suggested that the hydrogel devices synthesized with 27% water and filled with insulin‐loaded particles (120 IU) were able to control blood glucose levels for up to 5 days after implantation. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) graft copolymers and their application as carriers for drug delivery system

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) [P(NIPAM‐co‐HEMA)] copolymer was synthesized by controlled radical polymerization from respective N‐isopropylacrylamide (NIPAM) and hydroxyethyl methacrylate (HEMA) monomers with a predetermined ratio. To prepare the thermosensitive and biodegradable nanoparticles, new thermosensitive graft copolymer, poly(L ‐lactide)‐graft‐poly(N‐isoporylacrylamide‐co‐hydroxyethyl methacrylate) [PLLA‐g‐P(NIPAM‐co‐HEMA)], with the lower critical solution temperature (LCST) near the normal body temperature, was synthesized by ring opening polymerization of L ‐lactide in the presence of P(NIPAM‐co‐HEMA). The amphiphilic property of the graft copolymers was formed by the grafting of the PLLA hydrophobic chains onto the PNIPAM based hydrophilic backbone. Therefore, the graft copolymers can self‐assemble into uniformly spherical micelles ò about 150–240 nm in diameter as observed by the field emission scanning electron microscope and dynamic light scattering. Dexamethasone can be loaded into these nanostructures during dialysis with a relative high loading capacity and its in vitro release depends on temperature. Above the LCST, most of the drugs were released from the drug‐loaded micelles, whereas a large amount of drugs still remains in the micelles after 48 h below the LCST. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Syntheses,characterization, and antibacterial activity of chitosan grafted hydrogels and associated mica‐containing nanocomposite hydrogels

Chitosan (CS) grafted poly[(acrylic acid)‐co‐(2‐hydroxyethyl methacrylate)] (CS‐g‐poly(AA‐co‐HEMA)) at different molar ratios of AA and HEMA, and the associated nanocomposite hydrogels of CS‐g‐poly(AA‐co‐HEMA)/mica were synthesized by radical copolymerization. The grafting positions at the amino or hydroxyl groups in the CS were identified by Fourier transform infrared spectroscopy. CS‐g‐poly(AA‐co‐HEMA) hydrogels were intercalated in the mica and the amount of hydrogel insertion did not affect the spacing of the silicate layers in mica. The higher mica loadings produced a rougher surface of the nanocomposite hydrogel. The water absorbency of the CS‐g‐poly(AA‐co‐HEMA)/mica nanocomposite hydrogels decreased with increasing levels of mica loading to a lower level than those of the CS‐g‐poly(AA‐co‐HEMA) hydrogels. Both CS‐g‐poly(AA) and CS‐g‐poly(AA‐co‐HEMA)/mica nanocomposite hydrogels exhibited a higher antiproliferative activity against Staphylococcus aureus than did the neat CS hydrogel with CS‐g‐poly(AA) revealing a very pronounced minimum inhibition concentration (MIC) of 1.56 mg mL^?1. The extent of mica loading in the CS‐g‐poly(AA‐co‐HEMA) nanocomposite hydrogels did not affect the MIC (12.5 mg mL^?1). © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation and properties of modified PHEMA hydrogel with sulfonated PEG graft

A novel poly(ethylene glycol) (PEG) macromer with a methacryloyl and sulfonic acid group at each end of the chain was prepared. Modified hydroxyethyl methacrylate (HEMA) based hydrogels were synthesized by crosslinking polymerization of HEMA in the presence of the above‐mentioned PEG macromer. The effect of the sulfonated PEG graft was examined by comparing the swelling properties with those of a pure poly(hydroxyethyl methacrylate) (PHEMA) hydrogel. The modified PHEMA hydrogel exhibited increasing water absorbency with increasing sulfonated PEG content up to 15 wt %. These hydrogels with the sulfonated PEG graft exhibited a more hydrophilic character than the pure PHEMA gel. Also the swelling degree varied slightly with pH, showing increased swelling at higher pH probably due to the presence of the anionic sulfonate group on the PEG end chain. In addition, the protein adsorption test showed a lower level of fibrinogen adsorption from the sulfonated poly(ethylene glycol) (SPEG) modified gel than on the homo PHEMA hydrogel. Interestingly, scanning electron microscopy showed that the porous and rather uniform morphology of the gels changed with increasing sulfonated PEG content in PHEMA. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2484–2489, 2007     

Investigation of thermal behavior of poly(2‐hydroxyethyl methacrylate‐co‐itaconic acid) networks

The thermal behavior of poly(2‐hydroxyethyl methacrylate) [PHEMA] homopolymer and poly(2‐hydroxyethyl methacrylate‐co‐itaconic acid) [P(HEMA/IA)] copolymeric networks synthesized using a radiation‐induced polymerization technique was investigated by differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The glass‐transition temperature (T_g) of the PHEMA homopolymer was found to be 87°C. On the other hand, the T_g of the P(HEMA/IA) networks increased from 88°C to 117°C with an increasing amount of IA in the network system. The thermal degradation reaction mechanism of the P(HEMA/IA) networks was determined to be different from the PHEMA homopolymer, as confirmed by thermogravimetric analysis. It was observed that the initial thermal degradation temperature of these copolymeric networks increased from 271°C to 300°C with IA content. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1602–1607, 2007     

Preparation and characterization of nanostructured and high transparent hydrogel films with pH sensitivity and application

Novel nanostructured, high transparent, and pH sensitive poly(2‐hydroxyethyl methacrylate‐co‐methacryliac acid)/poly(vinyl alcohol) (P(HEMA‐co‐MA)/PVA) interpenetrating polymer network (IPN) hydrogel films were prepared by precipitation copolymerization of aqueous phase and sequential IPN technology. The first P(HEMA‐co‐MA) network was synthesized in aqueous solution of PVA, then followed by aldol condensation reaction, it formed multiple IPN nanostructured hydrogel film. The film samples were characterized by IR, SEM, DSC, and UV‐vis spectrum. The transmittance arrived at 93%. Swelling and deswelling behaviors showed the multiple IPN nanostuctured film had rapid response. The mechanical properties of all the IPN films improved than that of PVA film. Using crystal violet as a model drug, the release behaviors of the films were studied. The results showed that compared with PVA, which had low drug loading and exhibited high and burst release, the three IPN films had high drug loading and exhibited sustained release. Besides, the release followed different release mechanism at pH = 4.0 and pH = 7.4, respectively. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

A facile preparation of pH‐temperature dual stimuli‐responsive supramolecular hydrogel and its controllable drug release

A series of pH‐temperature dual stimuli‐responsive random copolymers poly[N,N‐dimethylaminoethyl methacrylate‐co‐poly(poly(ethylene glycol) methyl ether methacrylate][poly(DMAEMA‐co‐MPEGMA)] were synthesized by free radical polymerization. The supramolecular hydrogel was formed by pseudopolyrotaxane, which was prepared with the host‐guest interactions between α‐cyclodextrin (α‐CD) and poly(ethylene glycol) (PEG) side chains. Fourier transform infrared (FT‐IR), nuclear magnetic resonance (¹H NMR), and X‐ray diffraction (XRD) confirmed the structures of the hydrogels. The pH‐temperature dual stimuli responsive properties of the hydrogels were characterized by rheometer. Finally, the controllable drug release behavior of the hydrogel, which was used 5‐fluorouracil (5‐Fu) as the model drug, was investigated at different temperatures and different pH values. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43279.     

Synthesis and characterization of cholic acid‐containing biodegradable hydrogels by photoinduced copolymerization

A cholic acid (CA)‐containing biodegradable hydrogel (PLA‐PEG‐PLA‐co‐MACAH) was synthesized from the photoinduced copolymerization of a CA‐modified methacrylate monomer (MACAH), bearing a spacer of hexane‐1,6‐diol spacer between the methacryloyl and the cholanoate moieties, and a macromonomer (PLA‐PEG‐PLA‐DA), bearing two acryloyl end groups derived from a poly(lactic acid)‐b‐poly(ethylene glycol)‐b‐poly(lactic acid) triblock copolymer. The structure of MACAH was confirmed by FTIR, ¹H‐NMR, and MS. The hydrogel PLA‐PEG‐PLA‐co‐MACAH was characterized by scanning electron microscopy and X‐ray diffraction. The experiment results showed that the swelling ratios of the hydrogels decreased with the increase of the CA fraction. The investigation on the in vitro degradation of the hydrogel showed that the CA‐containing hydrogels degraded much slower than the hydrogels without CA component. The bioactivity of the synthesized hydrogels was assessed by the simulated body fluid method. The observed formation of hydroxyapatite on the scaffold of the hydrogels indicated that the hydrogels possess good bioactivity. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Laser scanning confocal microscopy versus scanning electron microscopy for characterization of polymer morphology: Sample preparation drastically distorts morphologies of poly(2‐hydroxyethyl methacrylate)‐based hydrogels

The internal morphologies for a series of heterogeneous PHEMA and P[HEMA‐co‐MeO‐PEGMA] [PHEMA = poly(2‐hydroxyethyl methacrylate), MeO‐PEGMA = poly(ethylene glycol) methyl ether methacrylate] hydrogels were characterized by scanning electron microscopy (SEM) in conjunction with a sample drying procedure, and by laser scanning confocal microscopy (LSCM) without prior drying. Compared to SEM, LSCM was far simpler and more rapid technique for imaging hydrogels. LSCM also allowed the native hydrated morphology of the hydrogels to be characterized, whereas SEM could only characterize the morphology of samples in their dehydrated state. No dehydration method used in this study preserved the true native morphology, but plunge freezing/freeze drying was the most suitable method that best preserved the native morphology for all hydrogel compositions. Refrigerated freezing/freeze‐drying and critical point drying introduced significant morphological artifacts, the severity of the artifacts being dependant on the sample's composition and Tg. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Synthesis,characterization, and in vitro release of ibuprofen from poly(MMA‐HEMA) copolymeric core–shell hydrogel microspheres for biomedical applications

This article describes the development of a new crosslinked poly(methyl methacrylate‐2‐hydroxyethyl methacrylate) copolymeric core–shell hydrogel microsphere incorporated with ibuprofen for potential applications in bone implants. Initially poly(methyl methacrylate) (PMMA) core microspheres were prepared by free‐radical initiation technique. On these core microspheres, 2‐hydroxyethyl methacrylate (HEMA) was polymerized by swelling PMMA microspheres with the HEMA monomer by using ascorbic acid and ammonium persulfate. Crosslinking monomers such as ethylene glycol dimethacrylate (EGDMA) has also been included along with HEMA for polymerization. By this technique, it was possible to obtain core–shell‐type microspheres. The core is a hard PMMA microsphere having a hydrophilic poly(HEMA) shell coat on it. These microspheres are highly hydrophilic as compared to PMMA microspheres. The size of the hydrogel microspheres almost doubled when swollen in benzyl alcohol. These microspheres were characterized by various techniques such as optical microscopy, scanning electron microscopy, Fourier‐transformed infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. The particle size of both microspheres was analyzed by using Malvern Master Sizer/E particle size analyzer. The in vitro release of ibuprofen from both microspheres showed near zero‐order patterns. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 3045–3054, 2002; DOI 10.1002/app.10310     

Novel dually responsive hydrogel with rapid deswelling rate

Hydrogels based on 2‐hydroxyethyl methacrylate (HEMA), methacrylic acid (MAA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) were prepared by free radical polymerization. The prepared hydrogels were characterized using Fourier transform infrared spectrometry. The states of water in the hydrogels were probed using differential scanning calorimetry and three types of water (free, freezing bound and non‐freezing bound) were detected, the contents of which were calculated. Compared with conventional poly(HEMA‐co‐MAA) hydrogels, the deswelling rate of the poly(HEMA‐co‐PEGMA‐co‐MAA) hydrogels is significantly improved, owing to the introduction of PEGMA. The deswelling process can be well described with a first‐order kinetics equation. Moreover, the swelling ratio of poly(HEMA‐co‐PEGMA‐co‐MAA) hydrogels exhibits a temperature dependence. Based on the analysis of the components of the hydrogels, a brushed core/shell structure is proposed for these, and confirmed by transmission electron microscopy observations. Copyright © 2006 Society of Chemical Industry     

Preparation and antidehydration of interpenetrating polymer network hydrogels based on 2‐hydroxyethyl methacrylate and N‐vinyl‐2‐pyrrolidone

This work reports the preparation of 2‐hydroxyethyl methacrylate (HEMA)/N‐vinyl‐2‐pyrrolidone (NVP) interpenetrating polymer network (IPN) hydrogels by UV‐initiated polymerization in the presence of free radical photoinitiator Darocur 1173 and cationic photoinitiator 4,4′‐dimethyl diphenyl iodonium hexafluorophosphate. The polymerization mechanism was investigated by the formation of gel network. The structure and morphology of the HEMA/NVP IPN hydrogels were characterized by fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The results showed that the IPN gels exhibited homogeneous morphology. The dehydration rates of HEMA/NVP IPN hydrogels were examined by the gravimetric method. The results revealed that the hydrogels had a significant improvement of antidehydration ability in comparison with poly(2‐hydroxyethyl methacrylate)(PHEMA) hydrogel embedded physically with poly(N‐vinyl‐2‐pyrrolidone)(PVP). © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and characterization of poly(HEMA‐co‐MMA)‐g‐POSS nanocomposites by combination of reversible addition fragmentation chain transfer polymerization and click chemistry

New hybrid poly(hydroxyethyl methacrylate‐co‐methyl methacrylate)‐g‐polyhedral oligosilsesquioxane [poly(HEMA‐co‐MMA)‐g‐POSS] nanocomposites were synthesized by the combination of reversible addition fragmentation chain transfer (RAFT) polymerization and click chemistry using a grafting to protocol. Initially, the random copolymer poly(HEMA‐co‐MMA) was prepared by RAFT polymerization of HEMA and MMA. Alkynyl side groups were introduced onto the polymeric backbones by esterification reaction between 4‐pentynoic acid and the hydroxyl groups on poly(HEMA‐co‐MMA). Azide‐substituted POSS (POSS? N₃) was prepared by the reaction of chloropropyl‐heptaisobutyl‐substituted POSS with NaN₃. The click reaction of poly(HEMA‐co‐MMA)‐alkyne and POSS? N₃ using CuBr/PMDEATA as a catalyst afforded poly(HEMA‐co‐MMA)‐g‐POSS. The structure of the organic/inorganic hybrid material was investigated by Fourier transformed infrared, ¹H‐NMR, and ²⁹Si‐NMR. The elemental mapping analysis of the hybrid using X‐ray photoelectron spectroscopy and EDX also suggest the formation of poly(HEMA‐co‐MMA)‐anchored POSS nanocomposites. The XRD spectrum of the nanocomposites gives evidence that the incorporation of POSS moiety leads to a hybrid physical structure. The morphological feature of the hybrid nanocomposites as captured by field emission scanning electron microscopy and transmission electron microscopic analyses indicate that a thick layer of polymer brushes was immobilized on the POSS cubic nanostructures. The gel permeation chromatography analysis of poly(HEMA‐co‐MMA) and poly(HEMA‐co‐MMA)‐g‐POSS further suggests the preparation of nanocomposites by the combination of RAFT and click chemistry. The thermogravimetric analysis revealed that the thermal property of the poly(HEMA‐co‐MMA) copolymer was significantly improved by the inclusion of POSS in the copolymer matrix. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Silicone hydrogels based on a novel amphiphilic poly(2‐methyl‐2‐oxazoline)‐b‐poly(dimethyl siloxane) copolymer

A novel amphiphilic hydrogel based on poly(2‐methyl‐2‐oxazoline)‐b‐poly(dimethyl siloxane) (PMeOx–PDMS) block copolymer was developed. First of all, PMeOx–PDMS macromonomer was synthesized by coupling mono‐hydroxylated PMeOx with PDMS followed by end‐capping with methacrylate group. The structures of each step were characterized by NMR and titration. After that, silicone hydrogels were prepared by UV‐initiated copolymerization of PMeOx–PDMS macromonomer with monomers such as 2‐hydroxyethyl methacrylate in the presence of a crosslinker. Measurements of the hydrogels' water contact angle, equilibrium water content, and tensile properties showed that the hydrogels possessed better hydrophilic surface, higher water content, and better ion permeability with the increase of the content of the macromonomer PMeOx–PDMS. Meanwhile, the tensile strength and Young's modulus of the hydrogels decreased slightly. Protein adsorption tests showed that the hydrogels had strong antifouling ability after the incorporation of PMeOx. This newly described hydrogel demonstrated attractive properties to serve as ophthalmic biomaterial. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39867.     

Physicochemical characterization of poly(ethylene glycol) plasticized poly(methyl vinyl ether‐co‐maleic acid) films

The influence of the poly(ethylene glycol) (PEG) plasticizer content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether‐co‐maleic acid) (PMVE/MA) was investigated with tensile mechanical testing, thermal analysis, and attenuated total reflectance/Fourier transform infrared spectroscopy. Unplasticized films and those containing high copolymer contents were very difficult to handle and proved difficult to test. PEG with a molecular weight of 200 Da was the most efficient plasticizer. However, films cast from aqueous blends containing 10% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 4 : 3 and those cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 2 : 1 possessed mechanical properties most closely mimicking those of a formulation we have used clinically in photodynamic therapy. Importantly, we found previously that films cast from aqueous blends containing 10% (w/w) PMVE/MA performed rather poorly in the clinical setting, where uptake of moisture from patients' skin led to reversion of the formulation to a thick gel. Consequently, we are now investigating films cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000, where the copolymer/plasticizer ratio is 2 : 1, as possible Food and Drug Administration approved replacements for our current formulation, which must currently be used only on a named patient basis as its plasticizer, tripropylene glycol methyl ether, is not currently available in pharmaceutical grade. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and application in drug controlled delivery of pH‐sensitive P(CE‐co‐DMAEMA‐co‐MEG) hydrogel

A pH‐sensitive hydrogel [P(CE‐co‐DMAEMA‐co‐MEG)] was synthesized by the free‐radical crosslinking polymerization of N,N‐dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG‐Mac) and methoxyl poly(ethylene glycol)‐poly(caprolactone)‐methacryloyl methchloride (PCE‐Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled‐release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non‐Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40737.     

Salt and pH sensitive semi‐interpenetrating polyelectrolyte hydrogels poly(HEMA‐co‐METAC)/PEG and its BSA adsorption behavior

A novel semi‐interpenetrating poly(2‐hydroxyethyl methacrylate) (pHEMA) based polyelectrolyte hydrogel [p(HEMA‐co‐METAC)/PEG] was prepared by copolymerizing HEMA with the cationic monomer 2‐methacryloyloxyethyltrimethyl ammonium chloride (METAC) in the presence of polyethylene glycol (PEG) with different content and molecular weight (MW 4000 and 400). The chemical structure of the gels was confirmed by FT‐IR spectroscopy, morphology study was performed by scanning electron microscope (SEM), thermal stability was revealed by thermogravimetric analysis (TGA), and the mechanical properties were determined by electronic universal testing machine. Swelling studies showed introduction of cationic monomer METAC led to high water content, and the obvious salt and pH sensitive properties were observed which proved the smart behavior of the semi‐interpenetrating polymer networks (IPNs) gels. In addition, the effect of temperature and some important biological solution on swelling behavior were reported. Cytotoxicity test demonstrated that synthesized gels owned satisfactory cytocompatibility and were convenient for the application as biomaterials. Finally, the weak bovine serum albumin (BSA) adsorption on semi‐IPNs by introducing METAC and controlling the content of PEG in gels demonstrated that they were of good protein resistance effect in biomedical applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41537.     

Effect of drug loading on the properties of temperature‐responsive polyester–poly(ethylene glycol)–polyester hydrogels

Hydrogels that can undergo gelation upon injection in vivo are promising systems for the site‐specific delivery of drugs. In particular, some thermo‐responsive gels require no chemical additives but simply gel in response to a change from a lower temperature to physiological temperature (37 °C). The gelation mechanism does not involve covalent bonds, and it is possible that incorporation of drugs into the hydrogel could disrupt gelation. We investigated the incorporation of drugs into thermo‐responsive hydrogels based on poly(?‐caprolactone‐co‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(?‐caprolactone‐co‐lactide) (PCLA–PEG–PCLA). Significant differences in properties and in the response to incorporation of the anti‐inflammatory drug celecoxib (CXB) were observed as the PEG block length was varied from 1500 to 3000 g mol^?1. Linear viscoelastic moduli of a PCLA–PEG–PCLA hydrogel containing a 2000 g mol^?1 PEG block were least affected by the incorporation of CXB and this gel also exhibited the slowest release of CXB, so the incorporation of phenylbutazone, methotrexate, ibuprofen, diclofenac and etodolac was also investigated for this hydrogel. Different drugs resulted in varying degrees of syneresis of the hydrogels, suggesting that they interact with the polymer networks in different ways. In addition, the drugs had varying effects on the viscoelastic and compressive moduli of the gels. The results showed that the effects of drug loading on the properties of thermo‐responsive hydrogels can be substantial and depend on the drug. For applications such as intra‐articular drug delivery, in which the mechanical properties of the hydrogel are important, these effects should thus be studied on a case‐by‐case basis. © 2019 Society of Chemical Industry