Preparation Of Amphiphilic Cyclodextrin Polymers And Study On Their Application As Drug Carriers

Amphiphilic copolymers play an important role in the field of drug delivery because they can load hydrophobic drugs to enhance their stability and bioavailability. In this paper, some new amphiphilic copolymers were synthesized by ring-opening polymerization of polysuccinimide (PSI) using the ethylenediamineanhydrous-β-cyclodextrin, and their feasibilities as vehicles for drugs were estimated.The main works of the thesis are as follows:1. Using water or pyridine as solvent, mono-6-(p-tolylsulfonyl)-β-CD (TsO-β-CD) was synthesized through the reaction between β-CD and p-toluenesulfonyl chloride in different ways. The influence of PH on the yield was discussed and the way to synthesize TsO-β-CD with a higher yield was received. Then ethylenediamineanhydrous-β-cyclodextrin was prepared through the reaction between TsO-β-CD and ethanediamine. PSI was synthesized by acid-catalysed polycondensation of L-aspartic acid in sulfolane. And three kinds of amphiphilic copolymers were synthesized by the ring opening polymerization of PSI using ethylenediamineanhydrous-β-cyclodextrin as initiator. Thses copolymers bear β-CD units along the macromolecular chain and different hydrophilic or hydrophobic monomer units. They are β-CD-g-PASP(copolymer Ⅰ), β-CD-benzyl-PEG-g-PASP(copolymer Ⅱ) and β-CD-phenylalanine-PEG-g-PASP(copolymer Ⅲ).Their structures were characterized by IR and 1HNMR.2. The amphiphilic copolymers micelles were prepared by direct dissolution method and dialysis method. Aggregation behaviors of the polymers were measured and the critical micelle concentrations(CMC) of the copolymers were measured by flourescence echnique using pyrene as probe. Morphological examination of the all the copolymers micells were performed using TEM. The results demonstrated that the copolymers could easily self-assemble into nanomicelles in water with low CMC and well size distribution. The TEM images indicated the presence of spherical particles with nanoscopic dimensions.3. Three kinds of drug-loaded micelles were prepared using methotrexate(MTX) as a model drug. The drug loading efficiency (DLE) were measrued and the drug release behaviors in vitro were investigated. The results demonstrated that the DLE of copolymer Ⅰ was about 10%, DLE of copolymer Ⅱ was about 20% and DLE of copolymerⅢ was about 18%. In PBS, the release profiles of MTX from the micelles solution were found to be slow steady releases which continued for more than two days. In which, the sustained release of copolymerⅡ was confirmed about 60 hours and the sustained release of copolymerⅢ lasted more than 120 hours.4. The three kinds of copolymers were respectively applied as carriers to encapsulate lutein, and the light stability of the encapsulated lutein were investigated. The results demonstrated that all copolymers can improved the light stability of lutein compared with β-CD.