Swelling and drug release properties of acrylamide/carboxymethyl cellulose networks formed by gamma irradiation

Hydrogels based on acrylamide monomer (AM) and different ratios (5–20 wt%) of carboxymethyl cellulose (CMC) were synthesized by gamma irradiation. The hydrogels were characterized in terms of gel content, swelling and drug release characters. The effect of temperature and pH on the degree of swelling was also studied. The results showed that the gel fraction of AM/CMC hydrogels decreases greatly with increasing the contents of CMC in the initial feeding solution. The kinetic study showed that the swelling of all the hydrogels tends to reach the equilibrium state after 5 h. However, the swelling of AM/CMC hydrogels was greater than the hydrogel based on pure AM. On the other hand, it was found that the swelling of all the hydrogels changes within the temperature range 30–40 °C and within the pH range 4–8. The AM/CMC hydrogels was evaluated for the possible use in drug delivery systems. In this respect, the release properties of methylene blue indicator, as a drug model, was investigated. It was found that the percentage release from the hydrogels increase with time to reach ～80% after 3 h at pH of 2 compared to ～100% at pH of 8.     

Physicochemical characterization and drug release properties of PDMAEMA/OSA Semi‐IPN hydrogels with microporous structure

A new poly(2‐(dimethylamino) ethyl methacrylate)/oxidized sodium alginate (PDMAEMA) semi‐interpenetrating network (Semi‐IPN) hydrogel with microporous structure was prepared by using PDMAEMA microgels as an additive during the polymerization/crosslinking process. The interior morphology characterized by scanning electron microscopy showed the Semi‐IPN hydrogels have different pore sizes by changing the amount of microgels. The hydrogels were also characterized by using Fourier transform infrared and DSC. The swelling behaviors of hydrogels indicated that the hydrogels have excellent pH and temperature sensitivity. Bovine serum albumin was entrapped in the hydrogels and the in vitro drug release profiles were established in different buffer solutions at various temperatures. The release behaviors of the model drug were dependent on the pore size of the hydrogels and environmental temperature/pH, which suggested that these materials have potential application as intelligent drug carriers. Copyright © 2011 John Wiley & Sons, Ltd.     

Poly(acrylamidoglycolic acid) nanocomposite hydrogels reinforced with cellulose nanocrystals for pH-sensitive controlled release of diclofenac sodium

In this study, a non-cytotoxic and pH-sensitive poly(acrylamidoglycolic acid) based nanocomposite (PAGA-NC) hydrogels reinforced with cellulose nanocrystals (CNCs) was synthesized using redox free radical polymerization. The successful formation and crystalline behaviour of PAGA-NC hydrogels was verified by fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analyses. The results showed that morphological, rheological and mechanical properties of the PAGA-NC hydrogels were strongly influenced by the CNCs content. Moreover, swelling properties were investigated, and the results suggested that they behaved as pH sensitive manner. The in vitro MTT assay showed that the PAGA-NC hydrogels are cytocompatibile to NIH-3T3 fibroblast cells. In addition, diclofenac sodium (DCF) model drug was successfully encapsulated into these PAGA-NC hydrogels via equilibrium swelling method. The in vitro release of DCF from PAGA-NC hydrogels was retained at pH 1.2 and maximum release was observed at 7.4, revealing as potential candidates for controlled release carriers for oral drug delivery applications.     

Synthesis and properties of biodegradable thermo- and pH-sensitive poly[(N-isopropylacrylamide)-co-(methacrylic acid)] hydrogels

Thermo- and pH-sensitive hydrogels were synthesized via the copolymerization of N-isopropylacrylamide (NIPAAm) and methacrylic acid (MAA) crosslinked with a biodegradable PEG-co-PCL macromolecular crosslinker under UV irradiation. Swelling measurements showed that temperature and pH sensitivity of the resultant hydrogels were highly dependent on the composition of the hydrogels as well as temperature and pH of the local medium. The pH and temperature dependence of the hydrogels displayed good reversibility. The hydrolytic degradation studies showed that the degradation rate of the hydrogels increased with the increasing content of MAA introduced in the hydrogels in pH 7.4 PBS solutions at 37 °C. The study on the release of BSA indicated that the release rate of BSA was higher at pH 7.4 than at pH 2.0, and increased with the increase of the MAA content in the hydrogels in pH 7.4 PBS solutions at 37 °C. These hydrogel materials are desirable for potential applications as smart drug delivery systems.     

Swelling and thermodynamic studies of temperature responsive 2-hydroxyethyl methacrylate/itaconic acid copolymeric hydrogels prepared via gamma radiation

The copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) were synthesized by gamma radiation induced radical polymerization. Swelling and thermodynamic properties of PHEMA and copolymeric P(HEMA/IA) hydrogels with different IA contents (2, 3.5 and 5 mol%) were studied in a wide pH and temperature range. Initial studies of so-prepared hydrogels show interesting pH and temperature sensitivity in swelling and drug release behavior. Special attention was devoted to temperature investigations around physiological temperature (37 °C), where small changes in temperature significantly influence swelling and drug release of these hydrogels. Due to maximum swelling of hydrogels around 40 °C, the P(HEMA/IA) hydrogel containing 5 mol% of IA without and with drug-antibiotic (gentamicin) were investigated at pH 7.40 and in the temperature range 25–42 °C, in order to evaluate their potential for medical applications.     

Synthesis and Evaluation of Biocompatible pH‐Sensitive Hydrogels as Colon‐Specific Drug Delivery Systems

Because of the growing importance of pH‐sensitive hydrogels as drug delivery systems, biocompatible copolymeric hydrogels based N‐vinyl‐2‐pyrrolidinone (NVP) and methacrylic acid (MAA) were designed and synthesized. These hydrogels were investigated for oral drug delivery. Radical copolymerizations of N‐vinyl‐2‐pyrrolidinone (NVP) and methacrylic acid (MAA) with the various ratios of cross‐linking agent were carried out at 70 °C. Azabisisobutyronitrile (AIBN) was the free‐radical initiator employed and Cubane‐1,4‐dicarboxylic acid (CDA) linked to two 2‐hydroxyethyl methacrylate (HEMA) group was the crosslinking agent (CA) used for hydrogel preparations. The hydrogels were characterized by differential scanning calorimetry and FT‐IR. Equilibrium swelling studies were carried out in enzyme‐free simulated gastric and intestinal fluids (SGF and SIF, respectively). A model drug, olsalazine [3,3′‐azobis (6‐hydroxy benzoic acid)] (OSZ) as an azo derivative of 5‐aminosalicylic acid (5‐ASA), was entrapped in these gels and the in‐vitro release profiles were established separately in both enzyme‐free SGF and SIF. The drug‐release profiles indicated that the amount of drug released depended on the degree of swelling. The swelling was modulated by the amount of crosslinking of the polymer bonded drug (PBDs) prepared. Based on the great difference in hydrolysis rates at pH 1 and 7.4, these pH‐sensitive hydrogels appear to be good candidates for colon‐specific drug delivery.     

壳聚糖-聚丙烯酸复合水凝胶的药物控制释放行为

以壳聚糖(Cs)和丙烯酸(AA)为原料,利用自由基聚合法制备了具有孔洞结构的复合水凝胶Cs-PAA,并研究了AA的量、交联剂的量、聚合温度和AA的中和度对水凝胶溶胀度的影响以及复合水凝胶对烟酸的控制释放。 结果表明,Cs-PAA复合水凝胶具有良好的pH值、离子强度敏感性,且溶胀度最高达1228 g/g,其在pH=686的缓冲溶液中的烟酸累积释放率明显大于其在pH=1.80的缓冲溶液,因此Cs-PAA水凝胶可作为肠口服药物的载体。     

Synthesis of hydrophilic microspheres with LCST close to body temperature for controlled dual‐sensitive drug release

Novel stimuli‐responsive hydrophilic microspheres were prepared by free radical polymerization of hydroxyethyl methacrylate (HEMA) and methacrylic acid (MA), as hydrophilic monomers, and N‐isopropylacrylamide (NIPAAm) and N,N′‐ethylenebisacrylamide (EBA), as thermo‐sensitive monomer and crosslinker, respectively. Hydrophilic comonomers were introduced in the macromolecular network to synthesize materials with tunable thermal behavior. In addition, by introducing in the polymerization feed both a hydrophilic and a pH‐sensitive monomer, such as MA, dual stimuli‐responsive (pH and temperature) hydrogels were synthesized. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and the shape of hydrogels was found to strictly depend on the concentration of monomers in the polymerization feed. Thermal analyses showed negative thermo‐responsive behavior with pronounced water affinity of microspheres at a temperature lower than lower critical solution temperature (LCST). In our experiment, the LCST values of the hydrogels were in the range 34.6–37.5°C, close to the body temperature, and the amount of hydrophilic moieties in the polymeric network allows to collect shrinking/swelling transition temperatures higher than the LCST of NIPAAm homopolymers. In order to test the preformed materials as drug carriers, diclofenac diethylammonium salt (DDA) was chosen and drug entrapment percent was determined. Drug release profiles, in media at different temperature and pH, depend on hydrogels crosslinking degree and drug–bead interactions. By using semi‐empirical equations, the release mechanism was extensively studied and the diffusional contribute was evaluated. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and Characterization of Sterculia Gum Based pH Responsive Drug Delivery System for Use in Colon Cancer

The present study deals with the modification of sterculia gum to develop the novel colon specific delivery system for use in colon cancer. The sterculia and acrylic acid based hydrogels were synthesized and characterized with FTIR, SEMs, TGA and swelling behavior. Swelling studies of the hydrogels were carried out as a function of reaction parameters such as monomer concentration, initiator concentration, amount of sterculia gum and crosslinker concentration and nature of swelling mediums. Swelling kinetics of the hydrogels and in vitro release dynamics of anticancer model drug methotrexate from the hydrogels were studied to evaluate the swelling mechanism and drug release mechanism from the drug-loaded hydrogels. The values of diffusion exponent for the release of drug were 0.883, 0.910 and 0.787 in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively. The release of drug from the polymer matrix occurred through a non -Fickian type diffusion mechanism.     

Formulation of pH-sensitive aminated chitosan–gelatin crosslinked hydrogel for oral drug delivery

The objective of this study is to develop efficient pH-sensitive hydrogel based on aminated chitosan (AmCs) and gelatin (Gel) biopolymers for oral drug delivery. Herein, AmCs was chemically crosslinked with gelatin (Gel) biopolymer with different ratios, while their structures, thermal profiles and morphological properties were investigated by FTIR, TGA and SEM characterization tools, respectively. Moreover, gel-content, crosslinking density and rheological analysis were also performed. The results clarified that the developed AmCs-Gel crosslinked hydrogel displayed variable pH-sensitive swelling profiles. By increasing AmCs ratio, the swelling ratio was boosted at pH 1.2 and declined at pH 7.4. Besides, by increasing gelatin ratio in the hydrogel matrix, the loading efficiency of Oseltamivir phosphate (as a model of drug) was augmented and reached maximum value of 79.0% by AmCs-Gel (2:3) crosslinked hydrogel. The in vitro drug release profiles were investigated for 6 h in simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. Variable release profiles were realized depending on variation of AmCs and Gel ratios in the crosslinked hydrogel matrix. Finally, the formulated smart crosslinked AmCs-Gel hydrogels demonstrated acceptable biodegradability with no cellular toxicity, suggesting their applicability as pH-sensitive oral drug carriers.     

Preparation and characterization of hyaluronate-hydroxyethyl acrylate blend hydrogel for controlled release device

Hyaluronate-hydroxyethyl acrylate blend hydrogels were investigated as matrices for controlled release devices. Glycidyl methacrylate (GMA) derivatized HA (GMA-HA) was synthesized by coupling of GMA to HA in the presence of a suitable catalyst. These hydrogels were prepared by a free radical copolymerization of GMA-HA and hydroxyethyl acrylate. The water content of these hydrogels at equilibrium swelling in water (Ww) was 0.978+/-0.0073 (n=18); however, these hydrogel was mechanically tough and could be used as disk shape. The hydrogels swelling were found to depend on ionic strength and pH. The dried hydrogels quickly regained their original condition in water, and they swelled to more than 90% of its initial water contents after 30 min. This swelling-deswelling behavior was reproducible. The release of chlorpromazine HCl as a model cationic drug from the gels was suppressed significantly in water. The release increased with increasing the ionic strength and decreasing pH of bulk solutions.     

Radiation synthesis of poly[(dimethylaminoethyl methacrylate)-co-(ethyleneglycol dimethacrylate)] hydrogels and its application as a carrier for anticancer delivery

The use of hydrogels as carriers for anticancer delivery has been a subject of significant recent research. In our recent work, we have shown that diffusion-controlled delivery of flutamide from hydrogels containing poly (dimethylaminoethyl methacrylate (DMAEMA)/ethyleneglycol dimethacrylate (EGDMA)) can be possible and controlled by the three-dimensional structure. Hydrogels based essentially on dimethylaminoethyl methacrylate and different ratios of ethyleneglycol dimethacrylate monomers were synthesized using gamma radiation copolymerization. The influence of copolymer composition and pH value of the surrounding medium on swelling behavior into the glassy polymer were discussed. The results showed that the ratio of EGDMA in the comonomer feeding solution has a great effect on the gel fraction and water content in the final hydrogel. In this regard, it was observed that the increase of EGDMA ratio decreased these properties. The ability of the prepared copolymer to be used as drug carrier for anticancer drug-delivery system was estimated using flutamide as a model drug. In vitro drug-release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and DMAEMA content of hydrogel.     

Structure and swelling-release behaviour of poly(vinyl pyrrolidone) (PVP) and acrylic acid (AAc) copolymer hydrogels prepared by gamma irradiation

Copolymer network hydrogels were prepared by gamma irradiation of aqueous solutions of poly(vinyl pyrrolidone) (PVP) and acrylic acid monomer (AAc). The composition of the final hydrogels compared to the composition of the initial preparation solutions of hydrogels was determined. The chemical structure and nature of bonding was characterized by IR spectroscopy analysis, while the thermal durability of the prepared hydrogels was assessed by thermogravimetric analysis (TGA). The kinetic swelling in water and the pH-sensitivity of PVP/AAc copolymer hydrogels was studied. The drug release properties of PVP/AAc hydrogels taking methyl orange indicator as a drug model was investigated. The IR spectra indicate the formation of copolymer networks, whereas the TGA study showed that the PVP/AAc hydrogels possess higher thermal stability than pure PAAc and lower than PVP hydrogels. The kinetic swelling in water showed that all the hydrogels reached equilibrium after 24 h and that the degree of swelling increases with increasing the ratio of AAc in the initial feeding solutions. It was found that the degree of swelling of PVP/AAc hydrogels increases greatly within the pH range 4-7 depending on composition.     

β-环糊精交联聚丙烯酸水凝胶的合成及其药物控制释放研究

采用1,3-二环己基碳化二亚胺(DCC)为缩合剂,通过β环糊精与丙烯酸的酯化反应合成了不同取代度的丙烯酸β环糊精酯(βCD6A),以此为单体与丙烯酸通过氧化还原自由基引发聚合,合成出了不同交联密度和不同环糊精含量的新型水凝胶(AAβCD6A).溶胀实验表明,该类水凝胶均具有pH敏感性,溶胀动力学实验进一步对其机理进行了探讨.选择苯丁酸氮芥(CHL)作为模型药物,考察了不同pH下AAβCD6A水凝胶对药物释放行为的影响.结果表明,pH=6.8时药物释放率均大于pH=2.0时药物释放率,环糊精的存在表现出促释作用.     

Development of Antibacterial,Degradable and pH-Responsive Chitosan/Guar Gum/Polyvinyl Alcohol Blended Hydrogels for Wound Dressing

The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels’ crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker–Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R² = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.     

Methyl methacrylate-co-itaconic acid (MMA-co-IA) hydrogels for controlled drug delivery

In the present work methyl methacrylate-co-itaconic acid (MMA-co-IA) hydrogels were synthesized by free radical copolymerization of methyl methacrylate (MMA) and itaconic acid (IA) using ethylene glycol dimethacrylate (EGDMA) and methylene bisacrylamide (MBAAm) as crosslinkers and benzoyl peroxide as initiator. Selected samples were loaded with model drug lactulose. For the lactulose release, the effect of pH, monomeric compositions, degree of crosslinking were investigated. The release of lactulose was studied for 8 h period in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.0. The drug release data were fitted into various kinetics models like the zero order, first order, Higuchi and Peppas. The release kinetics of lactulose from MMA/IA hydrogels was found to be best described by the Peppas model. Results showed that drug release increased by increasing IA content in the hydrogels but the effect of changing of crosslinking ratio on drug release was not significant. The surface morphology of MMA/IA drug loaded hydrogel was studied by SEM which revealed uniform distribution of the drug in the hydrogels. In conclusion, it can be said that lactulose can be successfully incorporated into crosslinked MMA/IA hydrogels and its release can be modulated by changing the mole fraction of the acid component in the gels.     

A pH-Sensitive Hydrogel with Hydrophobic Association for Controlled Release of Poorly Water-Soluble Drugs

A novel pH-sensitive hydrogel has been developed by UV induced radical polymerization of acrylic acid (AA) and amphiphilic macromonomer polyethylene glycol monolaurylether monoacrylate (PEGLA) with crosslinker ethylene glycol dimethacrylate for controlled release of acyclovir, a poor water-soluble model drug. The swelling behavior was investigated in the buffer of different pH at I = 0.1 M, as well as in the ethanol/water mixture. The hydrophobic association formed by the hydrocarbon chains in PEGLA was found to dominate the swelling properties of the hydrogels with subordinate pH sensitivity due to the ionization of the AA segments. Therefore, the drug loading of acyclovir has been improved and the release rate of acyclovir was slowed down with increasing the PEGLA content in the hydrogels. By fitting the release data with Weibull equation, the acyclovir release kinetics was changed from the Fickian diffusion to an anomalous diffusion when the PEGLA content in the hydrogels was beyond 20 mol%.     

Radiation synthesis of acrylic acid/polyethyleneimine interpenetrating polymer networks (IPNs) hydrogels and its application as a carrier of atorvastatin drug for controlling cholesterol

Gamma irradiation was used to form interpenetrating polymer networks structure (IPNs) hydrogels based on different ratios of acrylic acid monomer (AAc) and polyethyleneimine (PEI). The property-behavior was characterized by IR spectroscopy, gel content, thermogravimetric analysis (TGA) and swelling in water at room temperature and different pH values. The AAc/PEI hydrogels were used as a carrier for atorvastatin drug, in which the uptake-release character was studied. The results showed that the gel content of AAc/PEI hydrogels decreased greatly with increasing the ratio of PEI in the initial feeding solution. The AAc/PEI hydrogels displayed pH-sensitive character. The drug uptake-release study indicated that AAc/PEI hydrogels possessed controlled release behavior and that the release process depends on pH. In this respect, the release of atorvastatin drug was significant in acidic medium.     

Development of temperature-responsive semi-IPN hydrogels from PVA-PNVC-PAm for controlled release of anti-cancer agent

A series of semi-interpenetrating polymeric network (semi-IPN) hydrogels were synthesized using poly(vinyl alcohol) (PVA), monomers N-vinylcaprolactam (NVC) acrylamide (Am), and cross-linker bis[2-methacryloyloxy] ethyl phosphate (BMEP). The hydrogels were synthesized by using free-radical polymerization using ammonium persulphate (APS) as an initiator at 60°C. The hydrogels were characterized by various techniques such as Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) to confirm the formation, crystallinity, and morphological behavior. The swelling behavior at various temperatures and pH conditions showed that the semi-IPN hydrogels were good candidates for temperature-responsive nature. 5-Flurouracil (FU), a model anticancer drug, was successfully encapsulated and the encapsulation efficiency was found in range of 50–74% for different hydrogels. Further, in-vitro release studies were performed to investigate the release mechanism. The cumulative release studies showed that the developed hydrogels are potentially efficient for the gastrointestinal drug delivery of FU.     

Preparation of fast response superabsorbent hydrogels by radiation polymerization and crosslinking of N-isopropylacrylamide in solution

Macroporous temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with high equilibrium swelling and fast response rates were obtained by a ⁶⁰Co γ- and electron beam (EB) irradiation of aqueous N-isopropylacrylamide (NIPAAm) monomer solutions. The effect of irradiation temperatures, the dose, the addition of a pore-forming agent on the swelling ratio, and the kinetics of swelling and shrinking of the PNIPAAm gels was studied. The gels synthesized above the LCST exhibited the highest equilibrium swelling (300–400) and fastest response rate measured by minutes. Scanning electron microscope (SEM) pictures revealed that the gels synthesized above the LCST have larger pores than those prepared at temperatures below the LCST. The gels showed a reversible response to cyclical changes in temperature and might be used in a pulsed drug delivery device. The gels synthesized above the LCST exhibited the highest testosterone propionate release.