Chitosan Based Supramolecular Assemblies As Carriers Of Drug And Natural Ingredients

Supramolecules have attracted much interest in the past century due to their promising applications in diverse fields such as biomedicine, material preparation. In respond to the need of efficiently conversing chitosan to value-added products, this thesis is mainly focused on the design and preparation of chitosan based supramolecular assemblies with specific functions. One enzyme responsive drug loaded chitosan micelles system and three antioxidant systems with loading different liposoluble natural active ingredients were developed. The optimum encapsulation conditions of chitosan based supramolecular assemblies were investigated. Additionally, in vitro drug release behaviors and antioxidant activities of the drug loaded supramoleculars were also studied. These prepared materials have the potential to be used as active targeting drug formulations for cancer, functional food and cosmetics additives. Specifically, the thesis includes the following four parts:1. GRRGG recognition sequence of cathepsin B was used to connect hydrophilic chitosan quaternary ammonium salt(QCS) and hydrophobic polylactide(PLA) via amidation reaction. The obtained amphiphilic chitosan based copolymer(QGP) was able to self-assemble into micelles in aqueous solution at low concentration of 0.045 mg/m L. The QGP micelles can efficiently encapsulate liposoluble anticancer drug curcumin(Cur), and the solubility of Cur in QGP solution was up to 125.4 ± 5.2 μg/m L. In the study of in vitro drug release behavior, the QGP micelles loading Cur exhibited good enzyme sensitivity. These materials may possess vital reference value for active targeted therapy of cancer and are expected to be applied in the clinical treatment.2. A novel antioxidant chitosan based nanostructured materials were prepared by the entrapment of hydrophobic β-carotene(β-C) into chitosan graft polylactide(CS-g-PLA) micelles. The antioxidant activity and stability of β-C after encapsulation were investigated. It was found that the antioxidant activity of β-C can be effectively improved by CS-g-PLA nanomicelles encapsulation. The CS-g-PLA/β-C showed good physical stability and low degradation ratio during storage at 4oC and 25 oC for three months. These materials provide a kind of natural and effective stable carrier and aqueous dispersant for the fields of cosmetics and functional food.3. Antioxidant chitosan based systems containing vitamin E(VE) and Cur as single agents and in combination were designed by locating the two active ingredients into chitosan graft oleic acid(CSOA) micelles via microphase separation method. In compare with single encapsulation, the co-encapsulation of VE and Cur possessed improved entrapment efficiency values and stability, and exhibited better in vitro sustained release behaviors. Moreover, the antioxidant activities of VE and Cur as single agents or combinations after encapsulation appeared to be greatly enhanced.4. Chitosan based cyclodextrin supramoleculars composed of positively charged QCS and negatively charged carboxymethyl-β-cyclodextrin(CM-β-CD) were prepared for the encapsulation of a model drug, β-C. Compared with the free β-C, the obtained supramolecular assemblies were spherical particles and exhibited good aqueous dispersibility and improved antioxidant activities. The preparation method of these materials was simple and with low cost. This enabled to encapsulate other single of multiple natural active ingredients to obtain multifunctional materials.