Thermoresponsive drug controlled release from chitosan-based hydrogel embedded with poly(N -isopropylacrylamide) nanogels (original) (raw)
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e-Polymers, 2007
A novel kind of thermo and pH-responsive hydrogels was prepared by reacting N,O-carboxymethyl chitosan (NOCC) with amino-telechelic poly(Nisopropylacrylamide) (PNIPAAm-NH2) as a drug delivery carrier. The hydrogels were characterized by FT-IR and 1H-NMR techniques. The phase transition behavior of the hydrogels was found to be dependent on the NOCC/PNIPAAm-NH2 weight ratio and pH value of the medium. The hydrogels with a higher content of PNIPAAm showed a definite phase transition at 32 °C as it occurs in pure PNIPAAm. For the release study, NOCC-g-PNIPAAm beads were prepared using glutaraldehyde (GA) as a crosslinking agent. The swelling ratio of the beads was higher in pH 2.1 than pH 7.4. Moreover, the swelling ratio of the beads decreased with the increase in PNIPAAm content of the beads. The release profile of NOCCg- PNIPAAm beads showed a slower and controlled release of the entrapped ketoprofen, and found that the release behaviour was influenced by both the pH and temperature...
European Polymer Journal, 2005
Novel biodegradable pH-and thermal-responsive interpenetrating polymer network (IPN) hydrogels were prepared for controlled drug delivery studies. The IPN hydrogels were obtained in mild aqueous acid media by irradiation of solutions of N-acryloylglycine (NAGly) mixed with chitosan, in the presence of glutaraldehyde as a crosslinking agent and using 2,2-dimethoxy-2-phenyl acetophenone as photoinitiator. These hydrogels were subjected to equilibrium swelling studies at different temperatures (25°C, 37°C and 45°C) in buffer solutions of pH 2.1 and 7.4 (similar to that of gastric and intestinal fluids respectively). 5-Fluorouracil (5-FU) was entrapped in the hydrogels, and drug release studies carried out at 37°C in buffer solutions at pH 2.1 and 7.4.
Biomacromolecules, 2005
A series of hydrogels with both thermoresponsive and completely biodegradable properties was developed for aqueous encapsulation and controlled release of hydrophilic drugs in response to temperature change. The hydrogels were prepared in phosphate-buffered saline (pH 7.4) through free radical polymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-2-hydroxyethyl methacrylate units (Dex-lactateHEMA). Swelling measurement results demonstrated that four gels with feeding weight ratios of NIPAAm:Dex-lactateHEMA ) 7:2, 6:3, 5:4, and 4:5 (w/w) were thermoresponsive by showing a lower critical solution temperature at approximately 32°C. The swelling and degradation of the hydrogels strongly depended on temperature and hydrogel composition. An empirical mathematical model was established to describe the fast water absorption at the early stage and deswelling at the late stage of the hydrogels at 37°C. Two hydrophilic model drugs, methylene blue and bovine serum albumin, were loaded into the hydrogels during the synthesis process. The molecular size of the drugs, the hydrophilicity and degradation of the hydrogels, and temperature played important roles in controlling the drug release.
Journal of Applied Polymer Science, 2006
The aim of this study was to prepare and investigate the physical properties of a thermosensitive crosslinked chitosan pregel solution, and evaluate the in vitro release profiles of macromolecules from this sol-gel transition system. Chitosan and poly (vinyl alcohol) were used to form an interpenetrating polymeric network with glutaraldehyde as the crosslinker, and glycerophosphate (GP) was added to transform the pH-dependent solutions into thermosensitive pH-dependent solutions. Rheological study showed that the gelation was dependent on the crosslink degree and GP concentration of the solution. The crosslinked gel had excellent mechanic properties and no apparent "pores" and formed an integrated hydrogel texture according to scanning electronic micrograph. Gas chroma-tography test guaranteed the medication safety with no detection of glutaraldehyde remnants in the hydrogels. In vitro release study showed that the gelation does not significantly affect the macromolecules diffusion but the crosslinking degree does. These results indicated that the hydrogel formed an intensified three-dimensional hybrid network with interpenetrating molecules, which effectively buffered or delayed the macromolecules diffusion. The hydrogels sustained the drug release over 30 days and could be potentially used as in situ gelling implants.
Carbohydrate Polymers, 2017
Smart composite hydrogels (SCHs) consisting of chitosan (CS) microspheres physically embedded within a thermoresponsive hydrogel are synthesized and tested for their capacity of loading and long-term release of a small molecule drug. CS microspheres were used since they display pH-sensitive properties and have the capacity to bind electrostatically the opposite charged salicylic acid (SA), taken as model drug. These microspheres are ulterior physically entrapped within a thermoresponsive hydrogel based on poly(N-isopropylacrylamide-co-hydroxyethylacrylamide) copolymer, cross-linked with N,N-methylenebisacrylamide. The morphology, swelling behavior, temperature and pH sensitivity, degradability and drug release behavior of the new smart drug delivery system were investigated. Swelling ratios as well as the sharpness of the phase transition, largely depended on the cross-linking degree. The thermoresponsive network slightly protected the CS microspheres from the in vitro degradation. In vitro studies showed that the SA followed a prolonged release profile from SCHs in accordance with pH and temperature.
European Journal of Pharmaceutics and Biopharmaceutics, 2008
Temperature-sensitive hydrogels composed of poly(N-isopropylacrylamide) (PNIPAAm) with chitosan (CPN) and chitosan+hyaluronic acid (CPNHA) were grafted in order to examine their physicochemical characteristics, in vitro drug release, and in vivo pharmacodynamics. The sol-gel transition behavior was investigated by UV/visible spectrophotometry, differential scanning calorimetry, and viscometry. A slight difference in the transition temperatures was observed among these polymer systems, with CPN and CPNHA exhibiting higher temperatures compared with PNIPAAm. A zeta potential determination revealed a positive charge for the CPN hydrogel, whereas no or only a negligible charge was observed for PNIPAAm and CPNHA. The entanglement of CPN hydrogels observed using scanning electronic microscopy showed the densest cross-linkage structure, followed by CPNHA and PNIPAAm. Both hydrophilic and lipophilic drugs, including nalbuphine, indomethacin, and the nalbuphine prodrug, were used as model drugs in an in vitro drug release experiment. All 3 hydrogels significantly prolonged drug release. The release rate of hydrophilic nalbuphine increased in the order CPN<CPNHA<PNIPAAm. The drug release of these hydrogels exhibited a trend opposite to that of lipophilic drugs. A cold ethanol tail-flick study was utilized in order to examine the antinociceptive activity of intravenous nalbuphine. CPN and CPNHA prolonged the analgesic duration of nalbuphine with no influence on the onset time. The loading of nalbuphine in the CPNHA hydrogel exhibited the longest analgesic duration (4h) among the 3 hydrogels tested.
Polymers for Advanced Technologies, 2004
N-Isopropylacrylamide/itaconic acid copolymeric hydrogels were prepared by irradiation of the ternary mixtures of N-isopropylacrylamide/itaconic acid/water by c-rays at ambient temperature. The dependence of swelling properties and phase transitions on the comonomer concentration and temperature were investigated. The hydrogels showed both temperature and pH responses. The effect of comonomer concentration on the uptake and release behavior of the hydrogels was studied. Methylene blue (MB) was used as a model drug for the investigation of drug uptake and release behavior of the hydrogels. The release studies showed that the basic parameters affecting the drug release behavior of the hydrogels were pH and temperature of the solution.
Chitosan-based interpolymeric pH-responsive hydrogels forin vitro drug release
Journal of Applied Polymer Science, 2006
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 gammairradiation by different doses. The equilibrium swelling characteristics were investigated for the gels at 37 degrees 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 degrees 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.
Journal of Chemistry, 2020
In this study, chitosan-based hydrogels were produced by incorporating three drugs with a different solubility into a polymer matrix. The lyophilized chitosan salt was prepared using an innovative and less-expensive synthetic process by the freeze-drying technique. Firstly, the three drugs (caffeine, ascorbic acid, and 5-fluorouracil (5-FU)) were selected as model drugs to test the in vitro release behavior of the hydrogel. The drugs were solubilized in chitosan salt, lyophilized, and cross-linked with benzaldehyde involving the formation of a Schiff base with (–C=N-) linkage to produce a physical hydrogel. Subsequently, the physicochemical properties of N-benzyl chitosan and lyophilized chitosan salt were evaluated by Fourier-transform infrared (FTIR) spectra, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The intrinsic viscosity of the conventional chitosan was determined by the Mark–Houwink–Sakurada equation. Moreover, the kinetics of hydrogel swelling ...