Preparation And Micellization Of Chitosan-based Copolymers And Their In Vitro Drug Release Behaviors

In this thesis, several amphiphilic chitosan-based copolymers were synthesized through condensation method and their self-assembled (drug-loaded) micelles were prepared by dialysis method. The CMCs of these copolymers were determined by fluorescence probe techniques. Meanwhile, the physicochemical properties of these (drug-loaded) micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV-vis spectrometer respectively. Moreover, the effcts of cross-linked conditions on the micellar size were investigated. Then, the mixed micelles with active-targeting function were prepared by introducing the temperature-sensitive segments into the micelles. The main contents are summarized as follows:1. The amphiphilic graft copolymer CS-g-SA&PVP was synthesized and it had low CMC of 0.02 mg/ml. The copolymer can self-assemble to spheric micelles in water with the average diameter about 136.4 ran. The hydrophobic drug prednisone acetate (PA) used as a model drug was incorporated into the cores of the micelles and the drug-loading content (LC) and drug-loading efficiency (LE) of the drug-loaded micelles were 29.0 wt% and 82.0% respectively. The in vitro drug release behavior from the drug-loaded micelles exhibited initial burst release and then sustained drug release.2. The cross-linked micelles from CS-g-SA&PVP micelles were prepared used TPP as ionic cross-linked agent. The control experiments showed that when the concentration of CS-g-SA& PVP micelles was 1 mg/ml, the cross-linked micellar diameters increased with the increasing of TPP solution concentration and decreased with the increasing of PH (from 5.07 to 7.16) of TPP solution. The processes of cross-linking almost did't affect LC and LE. Moreover, the drug release behavior from drug-loaded cross-linked micelles exhibited obviously sustained drug release behavior without initial burst release. 3. Two amphiphilic graft copolymers PHCS-g-P(NIPAAm-co-DMA) and PHCS-g-PVP were successfully synthesized. The self-assembled micelles of the two copolymers were prepared and their mean diameters of the micelles were 183.6 and 119.1 nm respectively. Meanwhile, The lower critical solution temperature (LCST) of the PHCS-g-P (NIPAAm-co-DMA) micelles was 38.3℃. Based above, the mixed micells composed of PHCS-g-P(NIPAAm-co-DMA)/PHCS-g-PVP (w/w=7:3) were prepared. The CMC of the mixed copolymer is at the same order magnitude with that of the one-component copolymer (10-3). The mean micellar diameter and the LCST of the mixed micells are 165.4 nm and 39.6℃respectively. PA was loaded into the mixed micelles and the result showed the drug-loaded mixed micelles had LC of 22.70 wt％and LE of 73.0%. In addition, in vitro drug release behavior showed that the mixed micelles had temperature sensitiveness. These results showed that it can be used as a site-specific drug delivery triggered by the alteration of temperature.