Study On The Effect Of Structure Of O,O-diacyl Chitosan On The Drug Release Behavior Of Self-assembly Vesicles

Chitosan is a natural polysaccharide. Chitosan and its derivatives possess excellent biocompatibility, biodegradability and drug-absorbency enhancement. Their unique chemical and biological properties make them attractive materials for drug delivery system. By use of hydrophobic interaction of O, O-diacyl side chain, our research group has first prepared O, O-didodecanoyl chitosan self-assembly vesicles for drug delivery. On this basis, this paper mainly study the effect of chemical structure of O, O-diacyl chitosan, especially the acylation degree, length of O-acyl side chain and molecular weight of chitosans, and cholesterol on drug release behavior of the vesicles.O, O-dihexanoyl chitosan, O, O-dinonanoyl chitosan and O, O-didodecanoyl chitosan with difference acylation degrees are prepared by different molecular weight of chitosans, which are 3000 and 10000 Dalton respectively. The experimental results indicate that O, O-diacyl chitosan with difference acylation degrees can be prepared by control the proportion of reactants. The lower the length of acyl chloride or the smaller the molecular weight of chitosan is, the easier the reaction will take place.The morphology of O, O-diacyl chitosan vesicles is investigated by Scanning Electron Microscope (SEM). The experimental results show that the all kinds of O, O-diacyl chitosan self-assembly vesicles are spherical. The size distributions of the vesicles are among 100-300 nm.Vitamin B₁₂ is used as model drug for drug release study. The experimental results indicate that the drug-releasing rates and drug-releasing equilibrium ratios of vesicles made from higher degree of acylation, longer acyl chain and larger molecular weight of chitosan are lower. The vesicles with cholesterol have much bigger drug-releasing rates and drug-releasing equilibrium ratios. To add cholesterol to self-assembly materials can obviously cause the structure of the vesicles loose.The experimental results show that the drug-encapsulation efficiency of the vesicles without cholesterol is increased with increasing the degree of acylation, and the drug-loading of the vesicles is slightly decreased with increasing the degree of acylation. Both the drug-encapsulation efficiency and drug-loading of the vesicles without cholesterol are raised as the length of acyl chain and the molecular weight of chitosan enlarging. But the drug-encapsulation efficiency and drug-loading of the vesicles with cholesterol have not such changing rules.