Preparation and in-vitro evaluation of poly[N-vinyl-2-pyrrolidone-polyethylene glycol diacrylate]-chitosan interpolymeric pH-responsive hydrogels for oral drug delivery
Introduction
Recent years have witnessed significant advances made in the controlled drug delivery technology using polymeric hydrogels. Stimuli-responsive polymeric hydrogels, which swell or shrink in response to changes in the environmental conditions, have been extensively studied and used as smart materials for various biomedical applications (Peppas, 1997, Kurisawa et al., 1998, Langer, 1998). These polymeric hydrogels are being prepared from a limited number of synthetic polymers and their derivatives such as copolymers of methacrylic acid, acrylamide and N-isopropylacrylamide (Kopecek et al., 1971, Suzuki and Tanaka, 1990, Kokufuta et al., 1991, Kwon et al., 1991, Osada et al., 1992, Chen and Hoffman, 1995, Yoshida et al., 1995, Holtz and Asher, 1997). The design of a new biodegradable and biocompatible stimuli-sensitive polymeric systems play a key role in the development of multi-stimuli responsive biomaterials (Kurisawa and Yui, 1998).
Chitosan, a natural polysaccharide exhibits favorable biological properties such as biocompatibility, biodegradability and non-toxicity (Muzzarelli, 1977, Akbuga, 1995). For several years, chitosan has been largely evaluated as a potential vehicle for drugs administered orally. The development of hydrogel matrices incorporated with chitosan for oral drug delivery is still a virgin area of study. Hence the current investigation deals with the development of the new chitosan based hydrogel system for oral drug delivery to the stomach region.
Section snippets
Materials
NVP (Fluka, Buchs, Switzerland) was used as obtained. PAC was synthesized in the laboratory as reported earlier (Yamini et al., 1997). AIBN was a gift sample from Flex Carpets, Wellington, New Zealand and used after recrystallization from methanol. BIS (SERVA, Hiedelberg 1-Carl-Benz-Stra be 7, Germany), theophylline and 5-FU were from SIGMA, St. Loius, USA. Chitosan (catalogue number: 44,887-7, medium mol. wt.) was obtained from ALDRICH, Milwaukee, WI, USA and used without further purification.
Results and discussion
Chitosan, a natural polymer which exhibits pH sensitivity (Patel and Amiji, 1996) was chosen to develop interpolymeric hydrogels for oral controlled drug delivery to the stomach region in combination with NVP and PAC. Interpolymeric hydrogels are formed when two monomers are copolymerized in the presence of a polymer (Ravichandran et al., 1997). We expected a kind of intermixing of the polymeric systems to take place when these polymers are crosslinked to form polymeric networks. A totally new
Conclusion
A new pH responsive drug delivery system based on interpolymeric hydrogel, poly[NVP-PAC]-chitosan was developed for oral drug delivery. The preparation of these copolymeric hydrogels was carried out using a free-radical initiation technique. The equilibrium swelling measurements of these hydrogels carried out in simulated fluids clearly indicated the pH responsive nature of these hydrogels. The in-vitro release profiles of theophylline and 5-FU were established in SGF. This preliminary
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