Synihesisand Characterization Of Amphiphilic Graft Copolymers Of Pullulans Bearing Lactides Derivatives

As is known to all, amphiphilic copolymers can spontaneously self-assemble into nano-sizedaggregates in aqueous solution, such as micelle, vesicles, cylinders and other complex forms. Thesenanostructures which can be used as carriers have great potential applications in biomedical fields ofanticancer drug delivery, gene therapy and transfer, owing to their unique characteristics such as nanoscalesize, core–shell structure, relatively high stability and prolonged circulation in the blood. When the micelleparticles were used for anticancer drug delivery system, they can putt off the release of drug in the body,increase the solubility of drug, enhance the tumor targeting, and can reduce the toxicity of drug to normalcells, improve the utilization of drug. In the preparation of nanoparticles, the choice of the material ofcarrier is very important. Among a number of materials, the natural polysaccharide has unique advantagescompared with other materials, such as hydrophilicity, non-toxic, better biological compatibility andbiodegradable. But this kind of natural macromolecule material also has certain defects, and usually need tobe modified to satisfy various application. So, synthesis of functional amphiphilic polymers byhydrophobic modified polysaccharides and preparation of their self-assembled nanoparticles have drawnconsiderable interests. Pullulan polysaccharide has many merits. Firstly, it can stand acid, alkali, salt.Secondly, it is non-toxic, edible, highly hydrophilic, and it which has good blood compatibility can bedegraded. Moreover, there are a number of hydroxyl groups in the main chin of macromolecule so that canbe easily modified chemically. Therefore, pullulan and its derivative have received more investigativeinterests.Based on the background, this paper synthesizes a series of derivatives of hydrophobically modifiedpullulan by directly grafting different molecular weight and different optical rotation of polylactic acid(PLA) onto pullulan polysaccharides. The main research work of this paper is as follows:(1) First,5-hydroxymethyl-2,2,5-trimethyl-1,3-dioxane was prepared via the condensation reactionbetween2,2-dimethoxypropane and1,1,1-trimethylolethane using acetone as a solvent andp-toluenesulfonic acid as a catalyst. Next,2,2,5-trimethyl-5-methyl propargyl methoxyl-1,3-dioxane wassynthesized from the reaction of propargyl bromide and above condensation product. Then,2,2,5-trimethyl-5-methyl propargyl methoxyl-1,3-dioxane was deprotected under acidic condition to obtain 2-methyl-2-acetylene methoxyl-1,3-propanediol. Afterwards, a series of "V" type PLA with alkynyl weresynthesized by ROP of LA using2-methyl-2-acetylene methoxyl-1,3-propanediol as a initiator in thepresence oft Sn(Oct)2as a catalyst. The composition and structure of products were characterized by1Hnuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC).(2) The bromine atoms on the NBS substitute the hydroxyls on the6C of pullulan polysaccharidesbromide pullulan polysaccharides with DMF as solvent to obtain the pullulan-Br. Then, the pullulan-N3was synthesized from sodium azide and pullulan-Br. Finally,‘‘Click’’ reaction was adopted to immobilizethe alkyne of PLA onto the pendant azide group of pullulan which provided a relatively easy and efficientmethod to generate the target products of pullulan-g-PLA. The structure of polymers was characterized by1H nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FT-IR)and elementalanalyses.