Preparation and properties of temperature‐sensitive soy protein/poly(N‐isopropylacrylamide) interpenetrating polymer network hydrogels

Temperature‐sensitive interpenetrating polymer network (IPN) hydrogels based on soy protein and poly(N‐isopropylacrylamide) were successfully prepared. The structure and properties were systematically characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and thermogravimetric analysis, and the swelling and deswelling behavior was also investigated. It was found that the hydrogels had good miscibility, thermal stability and temperature sensitivity, and the lower critical solution temperature was ca 32 °C. Changing the content of soy protein or crosslinker could be used to control the swelling behavior, water retention and network structure of the IPN hydrogels. The results show that the novel IPN hydrogels may be of potential interest in drug delivery systems. Copyright © 2011 Society of Chemical Industry     

Preparation of alginate/poly(N‐isopropylacrylamide) semi‐interpenetrating and fully interpenetrating polymer network hydrogels with γ‐ray irradiation and their swelling behaviors

Semi‐interpenetrating polymer network (semi‐IPN) and fully interpenetrating polymer network (full‐IPN) hydrogels composed of alginate and poly(N‐isopropylacrylamide) were prepared with γ‐ray irradiation. The semi‐IPN hydrogels were prepared through the irradiation of a mixed solution composed of alginate and N‐isopropylacrylamide (NIPAAm) monomer to simultaneously achieve the polymerization and self‐crosslinking of NIPAAm. The full‐IPN hydrogels were formed through the immersion of the semi‐IPN film in a calcium‐ion solution. The results for the swelling and deswelling behaviors showed that the swelling ratio of semi‐IPN hydrogels was higher than that of full‐IPN hydrogels. A semi‐IPN hydrogel containing more alginate exhibited relatively rapid swelling and deswelling rates, whereas a full‐IPN hydrogel showed an adverse tendency. All the hydrogels with NIPAAm exhibited a change in the swelling ratio around 30–40°C, and full‐IPN hydrogels showed more sensitive and reversible behavior than semi‐IPN hydrogels under a stepwise stimulus. In addition, the swelling ratio of the hydrogels continuously increased with the pH values, and the swelling processes were proven to be repeatable with pH changes. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4439–4446, 2006     

Synthesis and characterization of fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels

BACKGROUND: A considerable amount of research has been focused on smart hydrogels that can respond to external environmental stimuli, especially temperature and pH. In this study, fast responsive thermo‐ and pH‐sensitive poly[(N,N‐diethylacrylamide)‐co‐(acrylic acid)] hydrogels were prepared by free radical copolymerization in aqueous solution using poly(ethylene glycol) (PEG) as a pore‐forming agent. RESULTS: Swelling studies showed that the hydrogels produced had both temperature and pH sensitivity. The deswelling kinetics at high temperature demonstrated that the shrinking rates were influenced by the addition of the pore‐forming agent and the amount of acrylic acid in the initial total monomers. The deswelling curves in low‐buffer solutions had two stages. Pulsatile swelling studies indicated that the PEG‐modified hydrogels were superior to the normal ones. These different swelling properties were further confirmed by the results of scanning electron microscopy. CONCLUSION: Such fast responsive thermo‐ and pH‐sensitive hydrogels are expected to be useful in biomedical fields for stimuli‐responsive drug delivery systems. Copyright © 2008 Society of Chemical Industry     

Preparation and characterization of pH‐ and temperature‐responsive semi–interpenetrating polymer network hydrogels based on linear sodium alginate and crosslinked poly(N‐isopropylacrylamide)

In this study, pH‐ and temperature‐responsive hydrogels based on linear sodium alginate (SA) and crosslinked poly(N‐isopropylacrylamide) (PNIPAAm) were prepared by semi‐interpenetrating network (semi‐IPN) technique. The dually responsive hydrogels were characterized by FTIR, DSC, and SEM, and their temperature‐ and pH‐responsive behaviors were investigated by measuring equilibrium swelling ratios and pulsatile swelling experiments. The results showed that these hydrogels underwent volume phase transition at around 33°C irrespective of the pH value of the medium, but their pH sensitivity was evident only below their volume phase transition temperature. Under basic conditions, the swelling ratios of SA/PNIPAAm semi‐IPN hydrogels were greater than that of pure PNIPAAm hydrogel and increased with increasing SA content incorporated into the hydrogels, but the case was inverse under acidic conditions. The pulsatile swelling experiments indicated that the higher the SA content in SA/PNIPAAm semi‐IPN hydrogels, the faster the response rate to both pH and temperature change. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1931–1940, 2005     

Photopolymerized pH‐sensitive semi‐IPN: Synthesis,water uptake analysis,and preliminary drug release study

A series of pH‐sensitive semi‐IPN hydrogels, composed of varying amounts of monomer acrylic acid(AAc), crosslinker N,N′ methylene bisacrylamide, polymer cellulose acetate (CA) were synthesized via photoinitiated polymerization in dimethyl formamide (DMF) medium. The CA/P (AAc) hydrogels were characterized by FTIR, and TG analysis. The equilibrium water uptake data was used to determine various network parameters. For all the samples synthesized, the swelling exponent “n,” initial diffusion coefficient D and average diffusion coefficient D_ave were found to be in the range of 0.51–0.72, 3.16 to 7.14 × 10^?6 cm² min^?1 and 94.16–120.56 cm² min^?1, respectively. The hydrogel demonstrated fair pH‐dependent swelling behavior, with nearly 20% swelling in the medium of pH 1.0 and 615% in the medium of pH 7.4 at 37°C, respectively. The gel showed excellent swelling–deswelling cycles which were interpreted quantitatively by first order kinetic swelling and deswelling models. Finally, the preliminary insulin release study, carried out in the media of varying pH, observed almost 16% release of entrapped drug in the simulating gastric fluid (SGF) of pH 1.0 in first 2 h and nearly 51% in next 6 h in simulating intestinal fluid(SIF) of pH 7.4 at 37°C. POLYM. ENG. SCI., 53:2129–2140, 2013. © 2013 Society of Plastics Engineers     

Synthesis and properties of the semi‐interpenetrating polymer network–like,thermosensitive poly(N‐isopropylacrylamide) hydrogel

A new strategy was used to prepare a semi‐interpenetrating polymer network (semi‐IPN)–like poly(N‐isopropylacrylamide) (PNIPAAm) polymeric hydrogel, consisting of either low (2300) or high (33,000) molecular weight linear PNIPAAm chains and the crosslinked PNIPAAm network. The properties of the resulting PNIPAAm hydrogels were characterized by DSC and SEM as well as their swelling ratios at various temperatures, the deswelling in hot water (48°C), and the oscillating shrinking–swelling properties within small temperature cycles. It was found that the deswelling rate of these semi‐IPN–like PNIPAAm hydrogels was improved if the molecular weight and/or composition of the linear PNIPAAm chains within the semi‐IPN–like PNIPAAm hydrogels were increased. This improved deswelling rate was attributed to the fast response nature of the linear PNIPAAm chains and the increased pore number in the matrix network, which provided numerous water channels for the water to diffuse out during the deswelling process at a temperature above the lower critical solution temperature. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1935–1941, 2003     

Indomethacin release behaviors from pH and thermoresponsive poly(vinyl alcohol) and poly(acrylic acid) IPN hydrogels for site-specific drug delivery

A temperature- and pH-responsive drug delivery system was studied by using interpenetrating polymer network (IPN) hydrogels constructed with poly(acrylic acid) (PAAc) and poly(vinyl alcohol) (PVA). The release of indomethacin incorporated into these hydrogels showed pulsatile patterns in response to both pH and temperature. Indomethacin diffused from the polymer matrices through the swelling and deswelling mechanism. The release amount increased at higher temperature because of the swelling caused by the dissociation of hydrogen bonding. The drastic change of drug release was achieved by alternating pH of the buffer solution and was attributed to the change of states of ionic groups within IPN hydrogels. The free water contents were calculated by using differential scanning calorimetry (DSC), and were proved to be the main factor in the swelling. These results demonstrated that the drug release could be controlled by the swelling/deswelling degree of IPN hydrogels as functions of pH and/or temperature. © 1997 John Wiley & Sons, Inc. J Appl Polm Sci 65: 685–693     

Preparation and characterization of a positive thermoresponsive hydrogel for drug loading and release

A positive thermoresponsive hydrogel composed of poly(acrylic acid)‐graft‐β‐cyclodextrin (PAAc‐g‐β‐CD) and polyacrylamide (PAAm) was synthesized with the sequential interpenetrating polymer network (IPN) method for the purpose of improving its loading and release of drugs. The structure and properties of the PAAc‐g‐β‐CD/PAAm hydrogel (IPN hydrogel) were characterized with Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and swelling measurements. FTIR studies showed that the IPN hydrogel was primarily composed of an IPN of PAAc‐g‐β‐CD and PAAm. The data from DSC and swelling measurements indicated that the phase‐transition temperature or upper critical solution temperature (UCST) of the IPN hydrogel was approximately 35°C. Through the measurement of the temperature dependence of the swelling, increases in the UCST and non‐sensitivity to changes in the salt concentration were observed for the IPN hydrogel versus the normal IPN hydrogel poly(acrylic acid)/PAAm (without β‐cyclodextrin). Furthermore, the swelling/deswelling kinetics of the IPN hydrogel also exhibited an improved controllable response rate versus the normal IPN hydrogel. Ibuprofen (IBU) was chosen as the model drug for examining loading and release from the IPN hydrogel. The experimental data proved that the IPN hydrogel provided a positive drug release pattern; the IBU released faster at 37°C than at 25°C, and improved drug loading and controlled release were achieved by the IPN hydrogel versus the normal IPN hydrogel. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

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     

A novel temperature and pH dual‐responsive hybrid hydrogel with polyhedral oligomeric silsesquioxane as crosslinker: synthesis,characterization and drug release properties

Octavinyl polyhedral oligomeric silsesquioxane (OVPS) is used as the crosslinker instead of N,N′‐methylenebisacrylamide (BIS) to copolymerize with 2‐(dimethylamino)ethyl methacrylate (DMAEMA) or DMAEMA and N‐isopropylacrylamide (NIPAM) to prepare hybrid hydrogels: P(OVPS‐co‐DMAEMA) and P(OVPS‐co‐DMAEMA‐co‐NIPAM). The prepared hydrogels are transparent and show dual response to temperature and pH. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, dynamic mechanical analysis and tensile tests. Their mechanical properties, swelling ratio, deswelling and reswelling behaviors as well as drug release properties were investigated. The results indicate that OVPS can be incorporated into polymer networks in proportion to feed ratios. The P(OVPS‐co‐DMAEMA) hydrogel exhibits more homogeneous interior structure, higher swelling ratio and faster response than the conventional hydrogel prepared with BIS. Moreover, the incorporation of OVPS enhances the compression and tensile properties of the hydrogels. The feed ratios of OVPS and NIPAM have a great effect on volume phase transition temperature, thermal sensitivity, swelling behavior, mechanical properties and drug release properties of the hybrid hydrogels. The prepared dual‐responsive OVPS‐containing hydrogels are expected to be used as biomedical materials in drug release and tissue engineering. © 2014 Society of Chemical Industry     

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     

Swelling behavior of thermoreversible poly(N‐isopropylacrylamide‐co‐N‐vinylimidazole) hydrogels

Thermoresponsive hydrogels based on N‐isopropylacrylamide and N‐vinylimidazole were synthesized, and their swelling–deswelling behavior was studied as a function of the total monomer concentration. For copolymeric structures with better thermoresponsive properties with respect to poly(N‐isopropylacrylamide‐co‐N‐vinylimidazole) hydrogels, these hydrogels were protonated with HCl and HNO₃, and the copolymer behaviors were compared with those of the unprotonated hydrogels. The temperature was changed from 4 to 70°C at fixed pHs and total ionic strengths. The equilibrium swelling ratio, dynamic swelling ratio, and dynamic deswelling ratio were evaluated for all the hydrogels. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1619–1624, 2004     

Dually responsive multinetworked hydrogels with improved performances by covalently bonding poly(N‐isopropylacrylamide)‐based microgels and poly(vinyl alcohol) skeleton

To prepare intelligent hydrogels with both good mechanical performance and fast response, a series of multinetworked composite hydrogels with pH and thermo‐responsivity were designed and fabricated combining the advantages of both interpenetrating polymer network hydrogels and microgels. To begin with, precipitation polymerization of N‐isopropylacrylamide, methacrylic acid and polyethyleneglycol methacrylate was carried out in poly(vinyl alcohol) (PVA) aqueous solution, yielding thermo‐ and pH‐responsive copolymeric microgels. Then glutaraldehyde was added to the obtained microgel dispersion to covalently bond the microgel particles and PVA through acetal reaction, leading to the formation of multinetworked hydrogels with dual responses. The morphology of microgels and the internal microstructure of composite hydrogels were characterized by transmission electron microscope and scanning electron microscope, respectively. The influence of the PVA content and glutaraldehyde dosage on the mechanical behavior of the prepared hydrogels was investigated by means of uniaxial compressive tests. Experimental results reveal that the as‐prepared composite hydrogels exhibit enhanced mechanical performance compared to conventional hydrogels. Investigation onthe swelling and deswelling behaviors shows that they possess good temperature‐ and pH‐sensitivity andswell/deswell more rapidly than conventional hydrogels. POLYM. COMPOS., 2012. © 2013 Society of Plastics Engineers     

Fast responsive poly(acrylic acid‐co‐N‐isopropyl acrylamide) hydrogels based on new crosslinker

Novel dual temperature‐ and pH‐sensitive poly(acrylic acid‐co‐N‐isopropylacrylamide), AA/NIPAAm, hydrogels were successfully prepared by chemical crosslinking with crosslinkers. Copolymers of AA/NIPAAm were crosslinked in the presence of different mol % of N,N‐methylene bisacrylamide (MBA) and melamine triacrylamide (MAAm) as crosslinkers by bulk radical polymerization. The resultant xerogels were characterized by extracting the soluble fractions and measuring the equilibrium water content. Lower critical solution transition temperatures (LCST) were measured by DSC. The properties of crosslinked AA/NIPAAm series are evaluated in terms of compositional drift of polymerization, heterogeneous crosslinking, and chemical structure of the relevant components. Soluble fractions of the crosslinked networks were reduced by varying the MAAm and MBA concentrations. The influence of environmental conditions such as temperature and pH on the swelling behavior of these polymeric gels was investigated. The swelling behaviors of the resulting gels show pH sensitivity. The prepared MAAm type AA/NIPAAm hydrogels exhibited a more rapid deswelling rate than MBA type AA/NIPAAm hydrogels in ultra pure water in response to abrupt changes from 20°C to 50°C. The results of this study provide valuable information regarding the development of dual stimuli‐sensitive hydrogels with fast responsiveness. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

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     

Photo‐cross‐linked biodegradable thermo‐ and pH‐responsive hydrogels for controlled drug release

A new strategy was developed to prepare thermo‐ and pH‐sensitive hydrogels by the crosslinking of poly(N‐isopropylacrylamide) with a biodegradable crosslinker derived from poly(L ‐glutamic acid). Hydrogels were fabricated by exposing aqueous solutions of precursor containing photoinitiator to UV light irradiation. The swelling behaviors of hydrogels at different temperatures, pHs, and ionic strengths were examined. The hydrogels shrank under acidic condition or at temperature above their collapse temperature and would swell in neutral or basic media or at lower temperature. These processes were reversible as the pH or temperature changed. All hydrogels exhibited no weight loss in the simulated gastric fluid but degraded rapidly in the simulated intestinal condition. Bovine serum albumin were used as a model protein drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and temperatures. The pH and temperature dependent release behaviors indicated the promising application of these materials as stimuli‐responsive drug delivery vehicles. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Thermo‐ and pH‐sensitive poly(vinylmethyl ether)/carboxymethylchitosan hydrogels crosslinked using electron beam irradiation or using glutaraldehyde as a crosslinker

BACKGROUND: Stimuli‐sensitive or intelligent hydrogels have been investigated for many biomedical and pharmaceutical applications. Those hydrogels with dual sensitivity will have more extensive potential applications. The aim of the work presented was to prepare a series of thermo‐ and pH‐sensitive hydrogels based on poly(vinylmethyl ether) (PVME) and carboxymethylchitosan (CMCS). The hydrogels were crosslinked using electron beam irradiation (EB) or using glutaraldehyde (GA) as a crosslinker at room temperature. RESULTS: The structures of the PVME/CMCS hydrogels obtained using the two crosslinking methods are proposed. The effects of component polymer ratio, GA content, irradiation dose, temperature and pH on the swelling behavior of the PVME/CMCS hydrogels were studied. There is a sharp decrease in the swelling ratios when the temperature increases from 25 to 37 °C. At low pH and also at high pH, the hydrogels have a higher swelling ratio; however, deswelling occurs evidently at a pH of around 3. CONCLUSION: The study shows that both EB and GA crosslinked hydrogels are thermo‐ and pH‐ sensitive, simultaneously. Thus, they may be potential candidates for both thermo‐ and pH‐sensitive applications. Copyright © 2009 Society of Chemical Industry     

Swelling behavior of semi‐interpenetrating polymer network hydrogels composed of poly(vinyl alcohol) and poly(acrylamide‐co‐sodium methacrylate)

Interpenetrating polymer network (IPN) hydrogels based on poly(vinyl alcohol) (PVA) and poly(acrylamide‐co‐sodium methacrylate) poly(AAm‐co‐SMA) were prepared by the semi IPN method. These IPN hydrogels were prepared by polymerizing aqueous solution of acrylamide and sodium methacrylate, using ammonium persulphate/N,N,N¹,N¹‐tetramethylethylenediamine (APS/TMEDA) initiating system and N,N¹‐methylene‐bisacrylamide (MBA) as a crosslinker in the presence of a host polymer, poly(vinyl alcohol). The influence of reaction conditions, such as the concentration of PVA, sodium methacrylate, crosslinker, initiator, and reaction temperature, on the swelling behavior of these IPNs was investigated in detail. The results showed that the IPN hydrogels exhibited different swelling behavior as the reaction conditions varied. To verify the structural difference in the IPN hydrogels, scanning electron microscopy (SEM) was used to identify the morphological changes in the IPN as the concentration of crosslinker varied. In addition to MBA, two other crosslinkers were also employed in the preparation of IPNs to illustrate the difference in their swelling phenomena. The swelling kinetics, equilibrium water content, and water transport mechanism of all the IPN hydrogels were investigated. IPN hydrogels being ionic in nature, the swelling behavior was significantly affected by environmental conditions, such as temperature, ionic strength, and pH of the swelling medium. Further, their swelling behavior was also examined in different physiological bio‐fluids. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 302–314, 2005     

Chitosan‐based interpolymeric pH‐responsive hydrogels for in vitro drug release

Two series of pH‐responsive biodegradable interpolymeric (IPN) hydrogels based on chitosan (Ch) and poly(vinyl alcohol) (PVA) were prepared for controlled drug release investigations. The first series was chemically crosslinked with different concentrations of glutaraldehyde and the second was crosslinked upon γ‐irradiation by different doses. The equilibrium swelling characteristics were investigated for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 as simulated gastric and intestinal fluids, respectively. 5‐Fluorouracil (FU) was entrapped in the hydrogels, as a model therapeutic agent, and the in vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4. FTIR, SEM, and X‐ray diffraction analyses were used to characterize and investigate the structural changes of the gels with the variation of the blend composition and crosslinker content before and after the drug loading. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2864–2874, 2007     

Swelling characteristics and in vitro drug release study with pH‐ and thermally sensitive hydrogels based on modified chitosan

The grafting of a poly(ethylene glycol) diacrylate macromer onto a chitosan backbone was carried out with different macromer concentrations. The grafting was achieved by (NH₄)₂Ce(NO₃)₆‐induced free‐radical poly merization. Biodegradable, pH‐ and thermally responsive hydrogels of poly(ethylene glycol)‐g‐chitosan crosslinked with a lower amount of glutaraldehyde were prepared for controlled drug release studies. Both the graft copolymers and the hydrogels were characterized with Fourier transform infrared, elemental analysis, and scanning electron microscopy. The obtained hydrogels were subjected to equilibrium swelling studies at different temperatures (25, 37, and 45°C) in buffer solutions of pHs 2.1 and 7.4 (similar to those of gastric and intestinal fluids, respectively). 5‐Fluorouracil was entrapped in these hydrogels, and equilibrium swelling studies were carried out for the drug‐entrapped gels at pHs 2.1 and 7.4 and 37°C. The in vitro release profile of the drug was established at 37°C and pHs 2.1 and 7.4. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 977–985, 2006