Synthesis And PH-sensitive Behavior Of Amphiphilic Block Copolymers

Amphiphilic block copolymers have many potential applications in fields such as drug delivery systems, surface modification of medical materials, microreactors and so on, due to their special properties. Recently, with the fast development of biological and medicine sciences, the preparations of biodegradable, biocompatible and stimuli-responsive micelles have become a new trend. In consideration of these demands, some polymers were selected to prepare the biodegradable, biocompatible and stimuli-responsive copolymer, and we studied its self-assembly behavior in a selective solvent, pH sensitivity and controll release behaviors.The main contents in this paper were as follows:1. A macro-chain transfer agent was prepared by the ring opening polymerization of lactide in the presence of hydroxyl-functional trithiocarbonate as a initator and stannous octoate as a catalyst, then chain extension of PLA via RAFT polymerization of N,N-dimethylamino-2-ethyl methacrylate(DMAEMA) resulted in the formation of PLA-b-PDMAEMA amphiphilic copolymer. The nuclear magnetic resonance spectroscopy (1HNMR and13CNMR) and fourier transform infrared spectroscopy (FT-IR) confirmed the composition and structure of PLA-b-PDMAEMA copolymers. The molecular weight and molecular weight distribution of polymers were analyzed by gel permeation chromatography measurements to confirm the diblock structure. The molecular weight of PLA19-b-PDMAEMA21and PLA19-b-PDMAEMA34were calculated by’HNMR to be6233g/mol and8217g/mol. But their molecular weights were lower by GPC than these measured by1HNMR, due to the adsorption effect of PDMAEMA and GPC column. The distribution coefficient of PLA-b-PDMAEMA was low comparatively. Besides, we used contact angle meter and thermogravimetric analysis to study the performance of copolymers, the results showed that the thermal stability and hydrophilicity of polylactide were improved due to the influence of PDMAEMA chain segment.2. In a selective solvent, PLA-b-PDMAEMA amphiphilic copolymers formed different structures of micelle due to copolymer composition, solution concentration, pH value and so on. Besides, Zetasizer Nano ZS90was used to study these different structures of micelle. The results indicated that at the same conditons the longer the hydrophilic segment was, the larger the micellar diameter was; the higher the concentration of polymer solution was, the larger the corresponding diameter was; in an acidic aqueous solution, the larger diameter of micelle was obtained due to the fully extended segments of PDMAEMA, on the contrary, the smaller diameter was obtained. In addition, aspirin was chosen as a model drug to study the drug loading and releasing behavior of the polymeric micelles, the results showed that under acidic conditions the drug-loaded micelles had a rapid rate of drug release, with the increase of pH value, the rate of drug release decreased; besides, the higher the amount of hydrophobic groups was, the lower the rate of drug release was.3. The shell cross-linked (SCL) micelles were prepared via shell crosslinking reaction between the PDMAEMA segments in the PLA-b-PDMAEMA micelles and1,2-bis-(2-iodoethoxy)ethane as a bifunctional crosslinking agent. Zetasizer Nano ZS90was used to study these different structures of micelles. In a selective solvent, we founded that the SCL micelles were swelling without dissolution, but the diameter of micelles without crosslinking decreased greatly, which confirmed the formation of SCL micelles. In addition, we founded that the sizes of micelle were different with different contents of crosslinking agent via Zetasizer Nano ZS90, the diameter of SCL micelles changed with the increase of the concentration of1,2-bis-(2-iodoethoxy) ethane, besides, SCL micelles had pH-responsive properties, in an acidic aqueous solution, the larger diameter of SCL micelle was obtained, on the contrary, the smaller diameter was obtained.In conclusion, the PLA-b-PDMAEMA micelles have pH sensitivity as drug carriers, the work will promote the application of the stimuli-responsive micelles in the medical field. Besides, the SCL micelles have a better stability and pH sensitivity, providing basis for SCL micelles as drug carriers in the future.