Quaternized Chitosan Based Amphiphilic Polymer Drug Delivery System: Synthesis And Characterization

Chitosan was used as the basic building block to synthesis a series of amphilic chitosan derivatives. Self-assembly behavior and the combination behavior with negative charged small molecule of the derivatives were studied.A novel convenient scheme was developed for synthesizing a novel series of chitosan-based graft copolymers. Sodium dodecyl sulfate-chitosan complex (SCC) was used as a precursor due to its organo-solubility. PCL was conjugated to the hydroxyl sites of SCC using common NCO coupling strategy. Decomplexation between SDS and CS gave CS-O-PCL. Futher trimethylation of CS-O-PCL gave TMC-O-PCL. The copolymers were characterized by FT-IR and1H NMR. Spherical micelles could be formed through dialyzing the copolyemer solution in DMSO against aqueous media. The self-assemble behavior of the copolyemrs was studied by fluorometry, TEM and DLS. The diameter was about30nm. The cytotoxicity of TMC-O-PCL micelles was evaluated using HepG2cells as model through MTT method. It was revealed that the cytotoxicity of the copolymers was affected by the trimethylation degree of the copolymer.Doxorubicin (DOX) was used as a model chemotherapeutic drug and the incorporation and in vitro release profile of DOX from TMC-O-PCL micelles were studied. It was found that the release behaviors were strongly dependent of the medium pH. When the medium pH decrease from7.4to5.0, the accumulated release arise about from45%to90%.Sulfate raffinose(OS) by sulphur trioxide pyridine complex to get a hydroxy group highly sulfated negative charged small molecule——raffinose sulfate(OSS). The polymers were characterized by FT-IR and1H NMR. HPLC result showed the scission of the glycosidic bond, and the content of target trisaccharide sulfate was above95%. OSS was coated to the positive charged shell of TMC-O-PCL micelle through electrostatic interaction, because they present opposite charge. The TMC-O-PCL micelle, which have the higher trimethylation degree, can combine more OSS and the combination was more steady.