Lactic Acid / Glycolic Acid Alternating Copolymer Synthesis, Characterization And Controlled Drug Release Applications

With good biocompatible and biodegradable proprieties, polyesters, such as polylactic acid (PLA), polyglycolic acid (PGA) and their copolymer PLGA were widely researched and used in medicine area, especially in controlled and prolonged release of drugs. But these polyesters still have some limitations described below: 1) PLA has poor affinity with antigens, polypeptides, and many hydrophilic low molecular drugs, because PLA is a much hydrophobic polymer. This physical property will limit its use in drug release fields. 2) It is very difficult to adjust the degradation period of PLA, because PLA degrades very slowly. 3) PGA is very difficult to fabricate, since it is insoluble in most commonly used organic solvents, such as chloroform, acetone, and methylene dichloride. PLGA50:50, which was approved by Food and Drug Administration (FDA), has poor solubility, too. Also, commonly used PLGA has no fixed chain and molecular structure, because it is a random copolymer (ran-PLGA).To overcome these limitations and to obtain a suitable drug excipient with good biocompatibility and biodegradability, an alternate copolymer of lactic acid and glycolic acid (alt-PLGA) was designed in this work. With a more hydrophilic GA chain in the molecular structure, alt-PLGA has a more hydrophilic property than PLA. At the same time, the introduced GA units in the macromolecular structure of alt-PLGA. will adjust the degradation time of the polymer. Because it has a fixed structure sequence, that is, a LA unit links to a GA unit alternately, this polymer has good reproducibility in physical and chemical properties. The same unit in the long chain as ran-PLGA ensures that alt-PLGA has the same biodegradability and biocompatibility as ran-PLGA. But the different structure sequence endues alt-PLGA different properties from ran-PLGA in physical and chemical characteristics, such as solubility, hydrophilicity and biodegradability.Our work of this paper was summarized below:1). Alt-PLGA was polymerized through the ring-opening polymerization of a six-member monomer, namely, 3-methyl-l,4-dioxane-2,5-dione (MDD). The structure of the monomer and the polymer, the influence factors of polymerization process were studied. Based on these studies, the polymerization mechanism was presumed.2). Alt-PLGA was studied as a matrix for drug controlled release. Microspheres containing Testosterone were prepared by a solvent-evaporation/ solvent-diffusion process. The influence factors of preparation process and drug release profile in vitro were studied, in comparison with PLA and ran-PLGA.3). e -Caprolactone ( e -CL) was used to modify the properties of alt-PLGA by co-polymerization method.