Preparation and characterization of 2‐hydroxyethyl methacrylate‐based porous copolymeric particles

2‐Hydroxyethyl methacrylate was copolymerized with three different comonomers, methyl methacrylate (MMA), styrene (St), and N‐vinyl‐2‐pyrrolidone (NVP), respectively, to prepare porous particles crosslinked using ethylene glycol dimethacrylate (EGDMA) in the presence of an organic solvent, 1‐octanol (porogen), by means of suspension copolymerization in an aqueous phase initiated by 2,2‐azobisisobutyronitrile. Nano‐pores were observed in the particles. The pore size and the swelling properties of these particles can be controlled by changing comonomers or adjusting the crosslinker or porogen concentration. A lower crosslinker or porogen concentration favors generating smaller pores, whereas a higher concentration of a hydrophilic comonomer, higher concentration of crosslinker, and higher porogen volume ratio promote the generation of larger pores. In addition, the effects of the porous characteristics on the swelling properties were explored. The swelling capacity of the porous particles is reduced with the increase in the crosslinker concentration; however, there is a critical porogen volume ratio, in which the maximal swelling capacity is reached. Higher porosity in the particles and higher amount of hydrophilic comonomer favor a higher swelling capacity of the particles. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Synthesis and characterization of polyacrylamide‐grafted chitosan hydrogel microspheres for the controlled release of indomethacin

Microspheres of polyacrylamide‐grafted‐chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti‐inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug‐entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug‐release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 μm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non‐Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug‐diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non‐Fickian trend and the diffusion was relaxation‐controlled. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1525–1536, 2003     

Swelling characterizations of chitosan and polyacrylonitrile semi‐interpenetrating polymer network hydrogels

Temperature‐ and pH‐responsive semi‐interpenetrating polymer network (semi‐IPN) hydrogels constructed with chitosan and polyacrylonitrile (PAN) were studied. The characterizations of semi‐IPN hydrogels were investigated using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). IPN hydrogels exhibited a relatively high swelling ratio, 23.31%–145.20% at room temperature. The swelling ratio of hydrogels depends on pH and temperature. DSC was used to determine the amount of free water in IPN hydrogels. The amount of free water increased with increasing chitosan content in the semi‐IPN hydrogels. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 2011–2015, 2003     

Preparation,characterization, and drug‐release properties of pH/temperature‐responsive poly(N‐isopropylacrylamide)/chitosan semi‐IPN hydrogel particles

Novel poly(N‐isopropylacrylamide) (PNIPAAm)/chitosan (CS) semi‐interpenetrating polymer network hydrogel particles were prepared by inverse suspension polymerization. The prepared particles were sensitive to both temperature and pH, and they had good reversibility in solution at different temperatures and pH values. The swelling ratios of PNIPAAm/CS hydrogel particles decreased slightly with the addition of CS, which did not shift the lower critical solution temperature. The drug‐release behavior of the particles was investigated using cyclic adenosine 3′,5′‐monophosphate (cAMP) as a model drug. The release of cAMP from the hydrogel particles was affected by temperature, pH, and the CS content in the particles. These results showed that semi‐IPN hydrogel particles appeared to be of great promise in pH‐ and temperature‐sensitive oral drug release. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Temperature sensitive semi‐IPN microspheres from sodium alginate and N‐isopropylacrylamide for controlled release of 5‐fluorouracil

Semi‐interpenetrating network (IPN) of sodium alginate (NaAlg) and N‐isopropylacrylamide (NIPAAm) microspheres were prepared by water‐in‐oil (w/o) emulsification method. The microspheres were encapsulated with 5‐fluorouracil (5‐FU) and release patterns carried in 7.4 pH at temperatures of 25 and 37°C. The semi‐IPN microspheres were characterized by Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry (DSC) and scanning electron microscopic studies were done on the drug‐loaded microspheres to confirm the polymorphism of 5‐FU and surface morphology of microspheres. These results indicated the molecular level dispersion of 5‐FU in the semi‐IPN microspheres. Particle size and size distribution were studied by laser light diffraction technique. Microspheres exhibited release of 5‐FU up to 12 h. The swelling studies were carried in 1.2 and 7.4 pH buffer media at 25 and 37°C. Drug release from NaAlg‐NIPAAm semi‐IPN microspheres at 25 and 37°C confirmed the thermosensitive nature by in vitro dissolution. The micro domains have released in a controlled manner due the presence of NIPAAm in the matrix. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

pH‐reversible hydrogels. IV. Swelling behavior of the 2‐hydroxyethyl methacrylate‐co‐acrylic acid‐co‐sodium acrylate copolymeric hydrogels

A series of 2‐hydroxyethyl methacrylate (HEMA) and sodium acrylate (SA50) copolymeric gels were prepared from HEMA and the anionic monomer SA50 with various molar ratios. The influence of SA50 on the copolymeric gels on their swelling behavior in deionized water at different temperatures and various pH buffer solutions was investigated. Results indicated that the poly(2‐hydroxyethyl methacrylate) (PHEMA) hydrogels exhibited an overshooting phenomenon in their dynamic swelling behavior. The maximum overshooting value decreased with increasing of the temperature. The same results were also found in the HEMA/SA50 copolymeric gels with a lower SA50 content. On the contrary, the overshooting phenomenon for HEMA/SA50 copolymeric gels with a higher content of SA50 was exhibited only under higher temperature (over 35°C). These copolymer gels were used to assess drug release and drug delivery in this article. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1360–1371, 2001     

Synthesis,characterization, and in vitro drug‐release properties of 2‐hydroxyethyl methacrylate copolymers

2‐Hydroxyethyl methacrylate was copolymerized with acrylamide, N‐vinyl‐2‐pyrrolidone, and n‐butyl methacrylate by free‐radical solution polymerization with α,α′‐azobisisobutyronitrile as an initiator at 70 ± 1°C. The average molecular weights and molar compositions of the resultant copolymers were determined with gel permeation chromatography and ¹H‐NMR spectroscopy data, respectively. Diclofenac or 2‐[(2,6‐dichlorophenyl)amino]benzene acetic acid, a nonsteroidal anti‐inflammatory drug, was chemically attached to the copolymers by transesterification reaction in the presence of N,N′‐dicyclohexylcarbodiimide to give macromolecular prodrugs. All the synthesized polymers were characterized with Fourier transform infrared, ¹H‐, and ¹³C‐NMR spectroscopy techniques. The polymer–drug conjugates were hydrolyzed in cellophane member dialysis bags containing aqueous buffered solutions (pH 8) at 37°C, and the hydrolysis solutions were detected by UV spectrophotometer at selected intervals. The results showed that the drug could be released by selective hydrolysis of the ester bond from the side chain of the drug moiety. The release profiles of the drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of the polymer. The results suggest that the synthesized copolymers could be useful carriers for the release of diclofenac in controlled‐release systems. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2403–2409, 2007     

Polymeric blend microspheres for controlled release of theophylline

Microspheres of poly(vinyl alcohol) (PVA) and hydroxyethyl cellulose (HEC) were prepared as semi‐interpenetrating networks (IPNs), crosslinked with glutaraldehyde and used in controlled release of theophylline (THP), an anti‐asthmatic drug. Formulations were characterized by X‐ray diffraction (XRD) to understand uniform distribution of THP, Fourier transform infrared (FTIR) spectroscopy to understand chemical interactions, universal testing machine (UTM) for mechanical stability, and scanning electron microscopy (SEM) for investigating the morphology of the microspheres produced. SEM indicated smooth surfaces of the microparticles and sizes of around 10–15 μm giving high encapsulation efficiency up to 69%. Equilibrium uptake performed in double distilled water and in vitro release studies performed in 1.2 and 7.4 pH buffer media indicated the effect of extent of crosslinking and HEC content of the semi‐IPN matrix on the release of THP that was extended up to 12 h. Analysis of in vitro results using empirical equation suggested a deviation from the Fickian transport. Drug diffusion was estimated from the Fick's diffusion equation for spherical geometry. Kinetics of drug release followed the Higuchi square root equation, indicating that release is diffusion‐controlled. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and swelling properties of pH‐sensitive hydrogels based on chitosan and poly(methacrylic acid) semi‐interpenetrating polymer network

A novel semi‐interpenetrating polymer network (semi‐IPN) hydrogel composed of chitosan and poly(methacrylic acid) was synthesized using formaldehyde as a crosslinker. The amount of crosslinker was searched and optimized. The structure of the hydogel was investigated by Fourier transform infrared (FTIR) spectroscopy. The spectrum shows that a structure of polyelectrolyte complex exists in the hydrogel. The effects of pH, ionic strength, and inorganic salt on the swelling behaviors of the hydrogel were studied. The results indicate the hydrogel has excellent pH sensitivity in the range of pH 1.40 to 4.50, pH reversible response between pH 1.80 and 6.80, and ionic strength reversible response between ionic strength 0.2 and 2.0M. The results also show that the hydrogel has a bit higher swelling capacity in a mix solution of calcium chloride (CaCl₂) and hydrochloric acid (HCl) solution than in a mix solution of sodium chloride (NaCl) and HCl. These results were further confirmed through morphological change measured by scanning electron microscope (SEM). © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1720–1726, 2005     

pH‐thermoreversible hydrogels. I. Synthesis and swelling behaviors of the (N‐isopropylacrylamide‐co‐acrylamide‐co‐2‐hydroxyethyl methacrylate) copolymeric hydrogels

A series of pH‐thermoreversible hydrogels that exhibited volume phase transition was synthesized by various molar ratios of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and 2‐hydroxyethyl methacrylate (HEMA). The influence of environmental conditions such as temperature and pH value on the swelling behavior of these copolymeric gels was investigated. Results showed that the hydrogels exhibited different equilibrium swelling ratios in different pH solutions. Amide groups could be hydrolyzed to form negatively charged carboxylate ion groups in their hydrophilic polymeric network in response to an external pH variation. The pH sensitivities of these gels also depended on the AAm content in the copolymeric gels; thus the greater the AAm content, the higher the pH sensitivity. These hydrogels, based on a temperature‐sensitive hydrogel, demonstrated a significant change of equilibrium swelling in aqueous media between a highly solvated, swollen gel state and a dehydrated network response to small variations of temperature. pH‐thermoreversible hydrogels were used for a study of the release of a model drug, caffeine, with changes in temperature. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 221–231, 1999     

Bioerodible hydrogels based on 2‐hydroxyethyl methacrylate: Synthesis and characterization

Biocompatible polymers with specific shape and tailored hydrogel properties were obtained by polymerization of mixtures of 2‐hydroxyethyl methacrylate (HEMA) with 1–8 wt % ethylene glycol dimethacrylate (EGDMA) or tetra(ethylene glycol) diacrylate (TEGDA) as crosslinking agents, by using a redox initiator. Introduction of charged positive and negative groups was easily achieved by direct polymerization of appropriate monomer mixtures and by chemical transformation of preformed hydrogels. Investigation of the swelling behavior of the prepared hydrogels evidenced an appreciable dependence on both solvent type and polymer chemical structure. Additionally, the solvation process resulted in being controlled by solvent diffusion, according to a Fickian II mechanism. The presence of several types of water with different melting behavior was observed in fully swollen hydrogels. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2729–2741, 2002     

Poly(2‐hydroxyethyl methacrylate‐co‐ethylene dimethacrylate) as a mouse embryonic stem cells support

A series of swellable ethylene dimethacrylate‐crosslinked poly(2‐hydroxyethyl methacrylate) (PHEMA) sheets of homogeneous (nonporous) structure or with different degrees of swelling and porosities was produced by bulk polymerization in either the absence or the presence of various diluents (porogens). Calculations performed by use of the solubility parameter δ of the reaction components indicate that the solvation conditions of the polymerization system change, depending on the solvating power of the diluent, which thus controls the porosity. Pore volume also seemed to be sensitive to the presence of the linear polymer diluent. Polystyrene (PS) showed, compared with poly(methyl methacrylate) (PMMA), a higher precipitating ability to form porous PHEMA sheets with an increased pore size because of its higher noncompatibility with newly formed crosslinked PHEMA. Given that PHEMA hydrogel is well known for its biocompatibility, it was used here as a potential carrier of cells in transplantation therapies. Attachment and growth of mouse embryonic stem (ES) cells on gelatin‐coated transparent PHEMA hydrogel substrates were examined. Two days after plating, survival and morphology of ES cells were largely similar on both PHEMA hydrogel sheets and in petri dishes as controls. This suggests that PHEMA hydrogels are likely candidates for application in transplantation therapies involving ES cells. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 425–432, 2003     

Synthesis and characteristics of semi‐interpenetrating polymer network hydrogels based on chitosan and poly(hydroxy ethyl methacrylate)

Semi‐interpenetrating polymer networks (semi‐IPNs), composed of chitosan and poly(hydroxy ethyl methacrylate) hydrogels, were prepared and the effects of various pH, temperatures, and an electric‐field on the swollen hydrogels were investigated. The swelling kinetics increased rapidly, reaching equilibrium within 60 min. Semi‐IPN hydrogels exhibited relatively high swelling ratios, 150～350%. The swelling ratio increased when the pH of the buffer was below pH 7 as a result of the dissociation of ionic bonds. Semi‐IPN hydrogels showed electroresponsiveness by shrinking when an electric field was applied. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 86–92, 2005     

Synthesis and swelling properties of 2‐hydroxyethyl methacrylate‐co‐1‐vinyl‐3‐(3‐sulfopropyl)imidazolium betaine hydrogels

A series of 2‐hydroxyethyl methacrylate/1‐vinyl‐3‐(3‐sulfopropyl)imidazolium betaine (HEMA/VSIB) copolymeric gels were prepared from various molar ratios of HEMA and the zwitterionic monomer VSIB. The influence of the amount of VSIB in copolymeric gels on their swelling behavior in water and various saline solutions at different temperatures and the drug‐release behavior, compression strength, and crosslinking density were investigated. Experimental results indicated that the PHEMA hydrogel and the lower VSIB content (3%) in the HEMA/VSIB gel exhibited an overshooting phenomenon in their dynamic swelling behavior, and the overshooting ratio decreased with increase of the temperature. In the equilibrium water content, the value increased with increase of the VSIB content in HEMA/VSIB hydrogels. In the saline solution, the water content for these gels was not affected by the ion concentration when the salt concentration was lower than the minimum salt concentration (MSC) of poly(VSIB). When the salt concentration was higher than the MSC of poly(VSIB), the deswelling behavior of the copolymeric gel was more effectively suppressed as more VSIB was added to the copolymeric gels. However, the swelling behavior of gels in KI, KBr, NaClO₄, and NaNO₃ solutions at a higher concentration would cause an antipolyelectrolyte phenomenon. Besides, the anion effects were larger than were the cation effects in the presence of a common anion (Cl^?) with different cations and a common cation (K⁺) with different anions for the hydrogel. In drug‐release behavior, the addition of VSIB increased the drug‐release ratio and the release rate. Finally, the addition of VSIB in the hydrogel improved the gel strength and crosslinking density of the gel. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 2888–2900, 2001     

New 2‐hydroxyethyl methacrylate resins with good swelling characteristics

2‐Hydroxyethyl methacrylate copolymers with styrene and series of the cross‐linkers (divinylbenzene and mono‐, di‐ and triethylene glycol dimethacrylates) with low cross‐linking degree (2–5 mol %) were obtained by suspension polymerization. Loading capacity of the resins, their glass transition temperature, and swelling characteristics in 20 solvents were analyzed depending on monomers composition. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1487–1493, 2006     

壳聚糖胶囊材料的制备及其缓释性能

采用壳聚糖为基材、果胶为交联剂制备了薄膜材料,考察了卡拉胶和淀粉为添加剂对该薄膜材料力学性能的影响。结果显示,不加卡拉胶、淀粉的果胶-壳聚糖复合聚合物薄膜材料由于不溶于模拟胃液和模拟肠液,不适合单独作为缓释胶囊材料。当加入卡拉胶和淀粉后,不仅可进一步增加薄膜材料的柔韧性、凝胶性、透明度和力学性能,还增加其在模拟肠液和胃液中的溶解性。果胶-壳聚糖、卡拉胶、淀粉的质量比为2∶1∶1,得到的薄膜材料不仅具有良好的成型性和弹性,也具有适中的胃液和肠液溶解性。将该材料制备成胶囊,在模拟胃液和模拟肠液环境考察其破壁缓释效果,结果显示,胶囊在模拟胃液和肠液中的溶解是一个缓慢过程,浸泡6h后,胶囊药物的缓释率大致为93%。     

Preparation and characterization of cyhalothrin‐loaded poly(2‐hydroxyethyl methacrylate)‐co‐polylactide (PHEMA‐co‐PLA) ultrafine particles

Poly(2‐hydroxyethyl methacrylate)‐co‐polylactide (PHEMA‐co‐PLA) and its corresponding cyhalothrin‐loaded ultrafine particles were successfully synthesized and prepared, respectively. The chemical structures of the copolymers have been confirmed by Fourier transform infrared spectroscopy (FTIR), ¹H‐nuclear magnetic resonance (¹H‐NMR), ¹³C‐nuclear magnetic resonance (¹³C‐NMR), and thermogravimetric analysis (TGA). Furthermore, the particle size, the cyhalothrin loading content (LC), and the cyhalothrin release behavior were investigated. PHEMA‐co‐PLA proved to be a good material for the preparation of ultrafine particles for lipophilic pesticide delivery. The developed cyhalothrin‐loaded PHEMA‐co‐PLA ultrafine particles showed good dispersity in water and sustained release behavior. In addition, it is easy to be prepared by both nanoprecipitation method and emulsion/solvent evaporation method. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation of porous chitosan/agarose microsphere and its R‐phycoerythrin release properties

The chitosan microspheres (CS‐CL) were prepared by suspension crosslinking method and used as carriers of R‐phycoerythrin (R‐PE). In this study, R‐PE was loaded in the microspheres and released in vitro. The effects of pH value, temperature, ionic strength, and R‐PE concentration on loading efficiency and release behavior were discussed. A novel microsphere that contained agarose (CS‐AR MP) was prepared and the basic loading and releasing behavior for R‐PE of this kind of new microspheres were also investigated. The results showed that all these chitosan microspheres have the ability to control‐release R‐PE. The addition of agarose may somewhat accelerate the release rate of R‐PE from microspheres and reduce the capacity of adsorption for R‐PE. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2759–2766, 2007     

Preparation of collagen‐immobilized poly(ethylene glycol)/poly(2‐hydroxyethyl methacrylate) interpenetrating network hydrogels for potential application of artificial cornea

To enhance the mechanical strength of poly(ethylene glycol)(PEG) gels and to provide functional groups for surface modification, we prepared interpenetrating (IPN) hydrogels by incorporating poly(2‐hydroxyethyl methacrylate)(PHEMA) inside PEG hydrogels. Formation of IPN hydrogels was confirmed by measuring the weight percent gain of the hydrogels after incorporation of PHEMA, as well as by ATR/FTIR analysis. Synthesis of IPN hydrogels with a high PHEMA content resulted in optically transparent and extensively crosslinked hydrogels with a lower water content and a 6 ～ 8‐fold improvement in mechanical properties than PEG hydrogels. Incorporation of less than 90 wt % PHEMA resulted in opaque hydrogels due to phase separation between water and PHEMA. To overcome the poor cell adhesion properties of the IPN hydrogels, collagen was covalently grafted to the surface of IPN hydrogels via carbamate linkages to hydroxyl groups in PHEMA. Resultant IPN hydrogels were proven to be noncytotoxic and cell adhesion study revealed that collagen immobilization resulted in a significant improvement of cell adhesion and spreading on the IPN hydrogel surfaces. The resultant IPN hydrogels were noncytotoxic, and a cell adhesion study revealed that collagen immobilization improved cell adhesion and spreading on the IPN hydrogel surfaces significantly. These results indicate that PEG/PHEMA IPN hydrogels are highly promising biomaterials that can be used in artificial corneas and a variety of other load‐bearing tissue engineering applications. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

In vitro degradation and protein release of semi‐IPN hydrogels consisted of poly(acrylic acid‐acrylamide‐methacrylate) and amylose

The enzymatic degradation mechanism of semi‐interpenetrating network (semi‐IPN) hydrogel of poly (acrylic acid‐acrylamide‐methacrylate) crosslinked by azocompound and amylose in vitro was investigated in the presence of Fungamyl 800L (α‐amylase) and rat cecum content (cecum bacteria). The degradation mechanism involves degradable competition, i.e., reduction of azo crosslinkage is dominant in the earlier period of degradation. Subsequently, the degradation of gels is continued by combination of reduction of azo crosslinkage and hydrolysis of amylose. The cumulative release ratios of Bovine serum albumin (BSA, as a model drug) loaded semi‐IPN gels are 25% in pH 2.2 buffer solutions and 74% in pH 7.4 buffer solutions within 48 h. Moreover, the release behavior of BSA from the semi‐IPN gels indicates that it follows Fickian diffusion mechanism in pH 2.2 media and non‐Fickian diffusion and polymer chains relaxation mechanism in pH 7.4 media. The results indicate that the release of BSA from the semi‐IPN gels was controlled via a combined mechanism of pH dependent swelling and specificity to enzymatic degradation. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007