Research On Lactic Acid Copolymers Containing The Structure Of 4-hydroxy Proline In The Backbone

Polylactic acid has been widely used as drug carriers for its well biodegradable and biocompatible properties. The feature of hydrophobicity and lack of functional groups for chemical reaction restricts its application. In this paper other monomers was troosed to copolymerizatoin with lactic acid for improving these properties.A series of copolymers were synthesized by direct melt copolymerization with stannous chloride as catalyst activated by a proton acid from lactic acid, glycolic acid, ethylene glycol and 4-hydroxy-proline(HPr) with the structure of 4-hydroxy-proline in the backbone. The synthesized copolymer was detected by infrared spectroscopy (IR), proton nuclear magnetic resonance (~1H-NMR) and differential scanning calorimeter(DSC). The optimum polymerization conditions was investigated. HPr can caused an increase in Tg and glycolic acid caused an decrease in Tg when increase the content, respectively. When the the glycolic acid content more than 70% or the content of HPr more than 10% the polymer changed from hemicrystalline to amorphous curves. The in vitro degradation rate of the PLGA-HPr copolymers is dependent on the feed ratio of the lactic and glycolic acids in the polymer chain.We synthesized the amphipathic polymer poly(lactic acid-4-hydroxy-proline-polyethylene glycol) (PLA-HPr-PEG), by the melt copolymerization with different content of PEG (0.1 wt%, 0.5wt%, 1.0wt%, 5.0wt%). The polymer was characterized by IR,~1H-NMR and DSC etc. The introduction of PEG could improve the hydrophilicity of the polymer and caused decreased in value of Tg. PEG rich polymer could lead to an accelerate degradation rate. 5-Fu loaded sub-microparticles were prepared by PLA-HPr-PEG. In the present work, the effects of the formulation variables on the prepared sub-microparticles were evaluated. As a result, PLA-HPr-PEG can control and release 5-Fu well and drug released by diffusion controlled mechanism. More PEG in PLA-HPr-PEG can promoting the drug release rate.PEG was used to improve the hydrophilicity of PLGA-Hpr. We synthesized series poly(lactic acid-glycolic acid-4-hydroxy-proiine-polyethylene glycol) (PLGA-Hpr-PEG) by direct melt polymerization. The structure and properties of these polymers were verified by IR, ~1H-NMR and DSC etc. The sub-microparticles of 5-Fu were made by PLGA-HPr-PEG. When the content of PEG is 5wt%, PLGA-HPr-PEG show a lower contact angle, a higher...