Study Of Degree Of Branching And Drug-Releasing Performance For ESO-Lactide Star Polymer

Epoxidized soybean oil (ESO) and lactide polymerization of epoxidized soybean oil - star-shaped polymer lactide (ESO-lactide) is a new bio-polymer material, whose molecular structure of space with more inclusive space and terminal functional groups, with good hydrophilicity. It can interact with many substances. Its structure, some physical and chemical nature, showed that ESO-lactide is a very good drug delivery carrier, but some troubles in physical-chemistry property aspects haven't been solved in the past. For example, the relationship of chemical structure and degradation and degradation mechanisms. The application is affected by these unsolved problems. Thus the further study of relationship between them and controlled-release performance of ESO-lactide star copolymer is important, which is helpful to the theoretical research and practical applications about long-chain branched polymers.This study involved the use of gel permeation chromatography coupled with eighteen angle laser scattering detector instrument (GPC-MALLS) to determine the degree of branching for ESO-lactide; studied its biodegradation laws; used ESO-lactide as the release material to prepare Levofloxacin/ ESO-lactide microspheres with multiple emulsion solvent evaporation method, and further study its drug release properties in vitro.The main research contents and conclusions are as follows:(1) Determination of the conditions of the optimization apparatus: apparatus is calibrated by Polystyrene(PS) standard sample (Mw : 3.0e+ 4 ), whose measure results are: Mn: 2.932e+4 (0.2%), Mw: 2.973e +4 (0.1%), Mz: 2.987e+4 (0.3%), respectively, which noted that credible degree reached 99.1% above, the instrument performance is stable, and the data is reliable. Temperature, flow rate, solution concentration, polymer dissolution time have important effects on the detection results of GPC-MALLS. The results of instrument, operating conditions showed that the satisfactory results were obtained , when solvent THF, polymer dissolution time is 8.5 h ,concentration of sample is 2.5mg/ml, flow rate is 1.0ml/min ,sample loop is 500μL and temperature is 34℃.(2) Degree of Branching Determination: the rotation rasius of the mean square(RMS) of poly (D, L-lactic acid) (PDLLA) and the ESO-lactide star polymer with close molecular weight were tested, which showed that the RMS of ESO-lactide star polymer was smaller, and then indicated the existence of branched structures, and with increasing of the number of ESO in the polymer, the molecular weight increased, radius of gyration decreased, degree of branching had increasing trend, that is, degree of branching is inversely proportional to branching parameters, and is proportional to the number of branches, molecular weight. Such as, the ESO-lactide star polymers with 0.3wt%,10wt% ESO with increased degree of branching increased, and branching parameters decreased.(3) Degradation properties: PDLLA, ESO-Lactide films were immersed in PBS buffer solution(PBS,pH=7.4), and degradation experiments were carried out at 37℃. The weight loss rates of samples during degradation were calculated, surface morphology and molecular weight of films before and after degradation were tested with SEM and GPC-MALLS, respective, the pH of degradation solutions at different degadation stages also were tested. The results showed that ESO-lactide has higher molecular weight and more branched structure than PDLLA, which resulted in the low degradation rate.(4) Preparation of Drug microspheres: according to orthogonal experiments, various influence factors, such as PVA, ESO-lactide concentration ,ratio of span-60 to tween-60, which effect on the properties of microspheres were examined. The results showed above three factors have significant effect on the microspheres. The preparation condition after optimization: ESO-Lactide concentration of 5%, PVA concentration of 1.5%, ratio of Span-60 to tween-60 of 3:1, which can produce micropheres with regular structure, small size and distribution uniformity. The levofloxacin/ESO-lactide microspheres, nice surface, good dispersion, an average particle size of 2000nm~4000nm, were prepared by using above preparation condition.(5) Drug release properties in vitro: the drug release properties of micropheres in vitro was investigated with dissolution, which showed that the cumulative release rate of levofloxacin / ESO-lactide microspheres is about 10% within 48 hours, and then indicated that levofloxacin / ESO-lactide microspheres have control-release function and can be used as release carrier for drug release. All above results showed that the determination of GPC-MALLS method of branching measure comparing with gel permeation chromatography-viscosity method can obtain reliable results. ESO-lactide has good biodegradation properties at PBS(pH=7.4), and it can be used as drug control-release material to preparate levofloxacin/ESO-lactide microspheres, which showed good drug release, thus ESO-lactide is hopeful to become a new star drug control-release material.