Abstract
The deacetylated form of chitin known as chitosan is currency been investigated due to its biodegradability, biocompatibility, non-toxic nature and its ability to form in situ gel with pH changes. Chitosan has also been shown to be mucoadhesive due to its polycationic nature. Hydrophobic lipids, such as glyceryl monooleate (GMO), have also been used as matrix material for sustained drug delivery of both hydrophilic and hydrophobic drugs. GMO forms liquid crystalline cubic phases in excess of water. This unique property of GMO is responsible for its bioadhesive property along with its ability to serve as a sustained release carrier for drug delivery. The objective of this study was to develop an in situ chitosan-GMO gel delivery system for sustained drug delivery. The good mucoadhesive property of this gel could be utilized as a targeting strategy.|The first part of the study focused on optimizing the delivery system with respect to the concentrations of chitosan and GMO. The optimum delivery system comprised of 3% (w/v) chitosan, 3% (w/v) GMO in 0.33 M citric acid. Drug was incorporated in the formulation and in situ gels were formed in Sorensen's phosphate buffer (pH=7.4) at 37°C. The delivery system was found to be pseudoplastic and hence can be used in parenteral delivery due to its shear-thinning nature. The in vitro drug release from such a gel was found to be quick.|Effects of cross-linking on the in vitro drug release from such a system were then investigated. Glutaraldehyde and DL-glyceraldehyde were employed as the cross-linkers. The effect of amount of cross-linking, its type, and reaction time (the elapsed time after addition of the cross-linker) were studied. Addition of cross-linker sustained the rate and extent of drug release of both hydrophilic and hydrophobic drugs. Reaction time with glutaraldehyde further retarded the drug release from such a gel system. Water uptake studies also revealed that increasing cross-linker concentration leads to lower water uptake into the system. This effect was non-significant after six hours of reaction indicating the completion of the cross-linking by six hours. The mechanism of drug release was found to be diffusion-controlled. Incorporation of a mixture of free drug and drug- loaded microspheres (prepared from ethylcellulose or poly (lactic-glycolic acid) in the formulation can also retard the release from such a system.|The mucoadhesive properties of this chitosan-GMO system were investigated using yield stress and peel strength determinations. The studies were carried out using an EZ-Tester and mucin type III as the substrate for mucoadhesion. Combination of chitosan and GMO, showed a 3-7 fold increase in the mucoadhesion.|In conclusion, the novel chitosan-GMO delivery system can be used both for oral and parenteral drug delivery to sustain the release of both hydrophilic and hydrophobic drugs. This enhanced mucoadhesive properties of this gel delivery system suggest that it might be for targeting of drugs where mucin is overexpressed (as in case of breast cancer).