Synthesis And Aggregation Characteristics Of Amphiphilic Copolymer N-maleoyl Chitosan-pluronic In Aqueous Solution

Amphiphilic copolymer N-maleoyl Chitosan-Pluronic (CMAP) was synthesized from thermo-sensitive Pluronic F127 and pH-sensitive Chitosan. The copolymer may increase the solubility of hydrophobic drugs and control their release in vivo due to the formation of self-assembled micelles, so it may be a type of novel superior drug carrier for sustained delivery of hydrophobic drugs. The following works have been done in the thesis:1. CMAP was synthesized through the reaction of Chitosan, maleic anhydride with Pluronic F127.1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (EDC·HCl) and N-hydroxysuccinimide (NHS) were proved to be the most appropriate reaction catalyzers. The product of CMAP was finally confirmed by IR analysis and 1H-NMR analysis.2. Dynamic light scattering (DLS), fluorescence measurement and viscosity method were used to investigate the characteristic of CMAP in the system. The result showed that the Molecular weight (Mr) of the CMAP was 79706 Da, and the Critical Micelle Concentration (CMC) of CMAP was 1.38×10-6 mol/l. The average size of CMAP micelles characterized by DLS was found to be 150 nm.3. The effects of temperature,pH value,solution concentration and different additives (such as NaCl, SDS, SDBS, CTAB and PEG-2000) on the aggregation properties and stability of polymer micelles were studied. The results showed that the mean size of micelle (from 150 nm to 320 nm) and solution viscosity incresed when NaCl was added in solution; the light scattering intensity of CMAP solution was increased along with the increase of the concentration of NaCl,then, the light scattering intensity of CMAP solution came down when the concentration of NaCl was high, which meant that NaCl at low concentration promoted micelles aggregation, while high NaCl concentration held back micelles aggregation. Adding a small amount of SDS to the CMAP solution could decrease the solution viscosity and light scattering intensity, then the viscosity and light scattering intensity of CMAP solution increased remarkably with the increase of the concentration of SDS; the average size of micelles increased from 150 nm to 320 nm. The SDBS showed the same impact on the polymer solution as the SDS did. The CTAB, a kind of cationic surfactant, decreased the light scattering intensity of solution, and prevented the polymer micelles from aggregating due to static repultion. The effect of of nonionic surfactant PEG-2000 on the solution was indistinctive. The above mentioned results demonstrated that the anionic surfactants could enlarge the micelles while the cationic surfactants showed abhorrent influence on micelles. It promoted micelles aggregating along with increased concentration of CMAP. The viscosity of CMAP solution reduced as the temperature increased. The pH value of solution remarkable influenced polymer micellar stability. The light scattering intensity of CMAP solution decreased obviously when the solution was in alkali condition, which meant that micelles were not stable. When the CMAP solution was acidic solution, the light scattering intensity of the solution increased obviously, and the micelles in the kind of solution tended to aggregate.