Synthesis Of Cylindrical Macromolecules As A Drug Controlled-release Material By Atom Transfer Radical Polymerization

Drug controlled-release materials are a class of drug carriers, entrapping drug with controllable release rates, mainly including liposomes, dendrimers, drug-polymer conjugates and polymeric micelles. To improve the therapeutic efficiency of loaded drugs, the drug carrier materials are supposed to have high drug loading capacities and encapsulation efficiencies, and possess a long blood circulation time. Up to date, these drug carriers based on hydrophobic association(e.g., liposome, microemulsion and nano-micelle) generally have shortcomings of low thermal stability, poor anti-dilution ability and difficult to control the drug release rate. In comparison with traditional spherical liposomes or micelles, rod or cylindrical micelles were recently found to have significantly prolonged blood circulation time and enhanced treatment efficiency. Atom transfer radical polymerization(ATRP) is a novel “living”/controlled radical polymerization technique and has been extensively used in the preparation of the graft, block, gradient, star, hyperbranched, dendritic and cylindrical macromolecules with well-defined architectures and narrow molecular weight distributions. In addition,ATRP has attracted much interest in biomedical materials due to its strong control and design of macromolecular architectures.This paper aimed to synthesize four cylindrical macromolecules with different molecular weights by ATRP and discussed the effects of polymerization kinetics and reaction conditions on the preparation of cylindrical macromolecules for employing them as drug carrier materials firstly. Then we loaded them with curcumin of anti-cancer activity to synthesize nano-capsules and then analyzed their drug loadings and encapsulation performances. The major work and research component of this thesis are as follows:1. Free radical polymerization was employed to synthesize polychloromethylstyrene(PCS) with some initiating sites(Cl), obtaining the narrow molecular weight distributions of macroinitiators PCS by precipitated and classified, and then the initiator PCS was used to initiate ATRP of Styrene(St) catalyzed by CuBr/Bpy. The results indicated that the macromolecular brushes PCS-St had symmetrical GPC peaks with low molecular weight distributions.2. The cylindrical macromolecules(PCS-St-Si-PEG) were synthesized by successful ATRP of 3-(trimethoxysilyl)propyl methacrylate and poly(ethylene glycol) methyl ether acrylate with PCS-St as initiators. The cylindrical macromolecules were examined by XRF and 1H NMR and calculated the molecular weights and compositions of the prepared polymers.3. The nano-capsules were formed from cylindrical macromolecules(PCS-St-Si-PEG or PCS-St-Si-PEG with curcumin) by dispension of the polymers or polymers with curcumin in water. The sizes and stability of the nano-capsules were subsequently measured. It was found that the nano-capsules respectively prepared from PCS-St-Si-PEG or PCS-St-Si-PEG with curcumin had narrow uniform size distributions and were well stability under some experimental conditions, indicating that nano-capsule was a stable nano-particle with narrow distribution.4. We applied the blank nano-capsules to load curcumin and analyzed their drug loadings and encapsulation efficiencies. The experimental results showed:(1) The drug loading and encapsulation efficiency of drug-loaded nano-capsules could reach 3.36% and 56.02% respectively;(2) The release of drug-loaded nano-capsules in vitro was a slow delivery process and the release rate would be lower when the cylindrical molecular weight increased. These results showed the cylindrical macromolecule is promising to be a novel drug delivery material.