The evaluation of biodegradable four star PEO-PLA copolymer as a drug delivery vector.

摘要

Current drug delivery vectors for sustained release include both naturally occurring and artificially synthesized polymers. Several linear copolymer systems have been explored for use as drug delivery systems because they form micelles and microspheres as a result of having hydrophobic and hydrophilic polymer portions. The pharmaceutical agent is released due to degradation of the polymer and/or by swelling of the polymer. This release is dependant upon the material containing the pharmaceutical agent; thus material design is a major parameter in establishing a drug delivery vector. Material design allows tailored physical and chemical characteristics, which are key to establishing release.; The overall goal of this research is to obtain and evaluate an unstudied branched Polyethylene glycol based polyether ester as a drug delivery vector through assessing and characterizing the micellar aggregation state, neat material thermal characteristics and morphology, micellar material degradation, effect of degradation on the micelle structure, and computational estimation of molecular aggregate force. This system may present enhanced physical properties for containing and delivering hydrophobic drug molecules due to its covalently linked branches.; Three constructs of four star polyethylene oxide polylactide copolymer were examined. The samples differed in molecular weight and chain length of the polylactide subunit and in stereo form. Characterization of micelles revealed that solubility decreased with increasing polylactide chain length and molecular aggregation in aqueous solution and that the critical micelle concentration was lower for the star system than for previously reported systems. Transmission electron microscopy and second virial calculations revealed polydispersity and batch to batch variation. Differential Scanning Calorimetry thermograms show two distinct transition peaks for the neat material samples. Thermogravimetric Analysis sample thermograms exhibited high thermal degradation temperatures. It was further observed that degradation time is proportional to polylactide chain length, that there was a change in intensity measurements of critical micelle concentration as degradation ensued, and that the size and shape of the micelles changed with degradation. Computational models of the neat polymer constructs and polymers in the presence of several water molecules were constructed and used to estimate the material's amorphous characteristics and molecular activity. Energy calculations suggest intra- and intermolecular aggregation.