Preparation Of Plymeric Antitumor Drug With Chitosan And Its Derivatives As The Carriers

In this dissertation, three water-soluble chitosan derivatives including carboxy-methylchitosan, hydroxyethyl Chitosan and N-Lactosaminated chitosan have been preparaed withchitosan of 100% degree of deacetylation (D.D) as raw material. Usinging the fullydeacetyled chitosan and its water-soluble derivatives as the carriers, norcantharidin, aneffective antitumor drug which has a rapid metabolism and strong urinary irration in vivo,was selected to be coupled with these carriers to obtained five types of polymer-drugconjugates attempting to prlong the metabolism, enhance the effectiveness and reduce thetoxicity. This work could provide a preliminary reference for the study of targeting,sustained and controlled release delivery systems of antitumor drug.First, the fully deacetyled chitosans with different Viscosity-average molecularweights (My) were prepared by an intermittent alkaline hydrolysis and degradation in thesystem of HAC /H₂O₂. Subsequently, the water-soluble chitosan derivatives mentionedabove were obtained from the fully deacetyled chitosan by different chemicalmodifications. The coupling reactions of chitosan and its water-soluble derivatives withnorcantharidin were further explored through a series of experiments. Ultimately, fourtypes of polymer-drug conjugate with different degrees of substitution (DS) weresuccessfully prepared. The DS of every chitosan derivative or polymer-drug conjugate wasdetermined by ¹H-NMR, elemental analysis or titration method.Chitosan-norcantharidin conjugate with higher DS was selected to perform a 10-daysanti-tumor experiment using the mice bearing H22 Hepatoma carcinoma cells as the model.The preliminary result indicated that chitosan-cantharidin had more powerfull antitumoreffect than norcantharidin or chitosan used solely. No apparent toxicity was found at lowor medium dosage.