GHRP-6温敏型凝胶的制备及其对小鼠生长的影响

Preparation of thermosensitive hydrogel containing growth hormone releasing peptide-6 and its effects on mice growth

采用开环聚合法合成PLGA—PEG-PLGA共聚物，制备GHRP-6温度敏感型缓释凝胶并对其体外释药和对小鼠生长的影响进行研究。以PLGA—PEpPLGA为载体材料制备GHRP一6缓释凝胶制剂，采用BCA法测定体外释放度，并对体外释放数据用Korsmeyer-Peppas方程进行拟合；分别对分组小鼠皮下注射GHRP-6凝胶（2．0g／L）、GH—RP-6（2．0g／L）、空胶和生理盐水，隔周称重。结果表明合成产物符合PLGA—PEG-PLGA共聚物的特征，质量分数为15％、20％、30％的共聚物水溶液的胶凝化温度在32～37℃；GHRP-6在浓度为15％、20％、25％共聚物中释放出95％以上的药物分别需要16、18、20d，其释放曲线均符合Korsmeyer-Peppas方程模型，且具有良好的相关性；各组小鼠在注射35d后，GHRP-6凝胶组的累积增重分别比生理盐水组、空胶组、GHRP-6组高45．18％（P〈0．01），39．090．4（P〈0．01），21．80％（P〈0．01）。由此表明GHRP一6在凝胶中的释放达到预期要求，且对小鼠的生长有显著的促进作用，因此GHRP-6的PLGA—PEGPLGA凝胶有望开发成为一种长效促生长的注射制剂。

The PLGA-PEG-PLGA copolymers were synthesized by ring-opening polymerization, preparing thermosensitive hydrogel for sustained release of growth hormone releasing peptide-6 in vitro and investigated its effects on mice growth. The thermosensitive PLGA-PEG-PLGA copoly- mers were used as the carriers of GHRP-6 sustained release. The release rate of GHRP-6 from the copolymer-based hydrogel was determined by BCA method. The data of release in vitro was ana- lyzed according to the theoretical model of Korsmeyer-Peppas. To study the effect on mice growth, mice were treated with GHRP-6 hydrogel（2.0 g/L）, GHRP-6 （2.0 g/L）, empty hygrogel and saline by subcutaneous injection, respectively, the body weight of each group was measured ev- ery week. The results showed that the synthetic product fits the characteristic of the PLGA-PEG- PLGA copolymer. The gelation tempreture of 15%, 20%, 30% copolymer solution was between 32℃ and 37℃. It needed 16,18,20 days respectively for over 95% of the GHRP-6 released from the concentration of 15%,20%,25% copolymer. The release data fitted to Korsmeyer-Peppas modeling and showed good correlation. After injected 35 days, the mean accumulative weight gain of mice injected with GHRP-6 hydrogel was 45.18%（P〈0.01）,39.09% （P〈0.01） ,21.80% （P〈0.01） higher than that of mice injected with saline, empty hydrogel and GHRP-6, respectively. The re- sults above indicate that the release of GHRP-6 in the gel meets the expected requirement,GHRP- 6 hydrogel could promote the growth of mice significantly. Therefore, PLGA-PEG-PLGAhydrogel containing GHRP-6 may develop into a kind of long term growth injection.