天門冬胺酸修飾PLGA-g-PEG高分子作為骨標靶奈米載體之合成與性質研究

Abstract

Controlled drug delivery technology represents one of the most important areas of science in which chemists are contributing to human health. Its purpose is to improved efficacy, reduced toxicity, and improved patient compliance and convenience. Two types of control over drug release can be achieved, temporal and distribution control. Because of musculoskeletal diseases have lacked of targeting drug delivery systems, result in delivering the drug not on correct part to cure. Using this drug more often than not only to treatment of these disease but brings other side effect. And water-insoluble drug unable to intravenous (IV) injection. Using oral medicine, in order to reach effective drug concentration, high systemic doses of the therapeutic must often administered, which may lead to significant adverse systemic and side effect. Taking medicine every day or inject therapeutic agent to patients of chronic musculoskeletal diseases for a long time, which influenced patient’s body, mind and live quality. Therefore, the newly bone-targeting drug delivery systems had developed. The carrier will pack fat-soluble drug and delivery to bone tissues exactly. The bone-targeting nanoparticles prepared from liner biopolymer PLGA and the end group to modified aspartic acid which is an amino acid and bone-targeting characterization. Achievement of initial, bone-targeting moiety aspartic acid was synthesized. Aspartic acid as initiator, methoxy protection group was modified. By protecting group the material was changed property which was organic solvent-insoluble. The derivation was reacted with PEG. In alkaline to remove the methoxy group. And the copolymer was conjugated to PLGA. PLGA-PEG-Aspn (n=1,3) triblock polymer was synthesized. The bone-targeting polymer identified with NMR, MASS, UV and IR. Nanoparticles size were prepared by dialysis and had size spread from 100 to 250nm. In vitro HAp affinity assay, the nanoparticles displayed bone-targeting efficiency than unmodified PLGA nanoparticles. Therefore, the development of bone-targeting drug delivery should have significant potential for treating musculoskeletal diseases future.