Synthesis Of β-cyclodextrin-grafted Sodium Alginate And Its Application In Controlled Release Drug Delivery System

Reasearches on new materials and controlled release system for durg delivery are always a fundamental approach to achieve the goals of improving release model, decreasing the toxicity, increasing the absorption and therapy effect. In this thesis, new controlled release material with both hydrophilic and hydrophobic properties was obtained by graftingβ-cyclodextrin onto the polymer chain of sodium alginate. The controlled release behavior of the new material was studied by using a model drug called as neutral red. The load effect and in vitro relese character show that this new matrial has suprior behaviors compared with that ofβ-cyclodextrin sodium alginate, suggesting the significance of potential application.The main work in the thesis includes the following four parts:(1) A new method for determing the accurate value of epoxy groups in aqueous solution was obtained by systemic investigation on the reaction between sodium sulfite and epichlorohydrin.(2) A new controlled release material ofβ-cyclodextrin grafted sodium alginate was obtained through epichlorohydrin linking. The reaction was studied under different conditions. There was nearly noβ-cyclodextrin linked to sodium alginate when without calcium chloride. The reason may be that the negative charge of carboxyl in sodium alginate affected the attachment of hydrogenoxide. After the addition of calcium chloride, carboxyls of sodium alginate reacted with calcium ions and the polymer chains were crosslinked. With the gel formation, the repelling effect of carboxyl in sodum alginate was greatly restrained and the grafting reaction was promoted. The results of ~1H NMR and IR spectra suggested thatβ-cyclodextrin grafted sodium alginate was obtained with the assistance of calcium chloride. The quantity ofβ-cyclodextrin grafted to sodium alginate was caculated by UV-vis spectrum study. When reaction was carried through at 70℃, the grafted amount ofβ-cyclodextrin can reach 16.6μmol/g of the sample。(3) In order to increase the content ofβ-cyclodextin in grafted sample, an activation grafting method was developed. Mono-tosyl-β-cyclodextin was synthesised by reactingβ-cyclodextrin with p-toluenesulfonyl chloride. Tetrabutylammonium alginate was synthesised by titrating tetrabutylammonium hydroxide solution into alginate acid, which was produced by reacting sodium alginate with hydrochloride.β-cyclodextrin grafted alginate was obtained by the reaction of mono-6-p-toluenesulfonyl-β-cyclodextrin with tetrabutylammonium of alginate acid in dimethyl sulfoxide. After purification, the sample was characterized by ~1H NMR and IR spectra. The content ofβ-cyclodextrin in the sample was 53.2μmol/g determined by UV-Vis method. This content is much higher than the reportedβ-cyclodextrin content (25.5μmol/g) linked to chitosan.(4) The controlled release character ofβ-cyclodextrin andβ-cyclodextrin grafted sodium alginate was studied by fluorescence method. The loading and in vitro release experiments were performed by using neutral red as a model durg. The results showed that the (neutral red) loaded amount, time of release, released concentration ofβ-cyclodextrin grafted sodium alginate/drug system were 23, 1.3, 30 times as high asβ-cyclodextrin system, respectively. Therefore,β-cyclodextrin grafted sodium alginate can be useful in developing a novel controlled delivery system to reach high performance for this kind of water soluble drugs.