Qiao Mingxi, Chen Dawei, Ma Xichen, Hu Haiyang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R. China.
Pharmazie. 2006 Mar;61(3):199-202.
Biodegradable thermosensitive poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with DL-lactide/glycolide molar ratio ranging from 6/1 to 15/1 were synthesized from monomers of DL-lactide, glycolide and polyethylene glycol and were evaluated for sustained release of bee venom peptide in vitro. The resulting copolymers are soluble in water to form free flowing fluid at room temperature but become hydrogels at body temperature. The gelation temperature of the copolymer solutions can be influenced by the concentration and DL-lactide/glycolide molar ratio of the copolymers. The release of bee venom peptide from the copolymer-based hydrogel and hydrogel degradation in the phosphate buffer (pH 7.4) was studied at 37 degrees C under agitation. Bee venom peptide was released from the copolymer-based hydrogels over 40 days in vitro and the variation of DL-lactide/glycolide molar ratio in the PLGA block of the copolymer did not significantly affect the release rate of bee venom peptide (P > 0.05). The hydrogels undergo slower degradation and then faster degradation rate during the whole release stage. Accordingly, the mechanism of bee venom peptide was Fickian diffusion during initial stage and then may be a combination of diffusion and degradation. The synthesized copolymers have the advantage of gelation temperature over the ReGel system. These results indicate that the PLGA-PEG-PLGA copolymer-based hydrogel could be a promising platform for sustained delivery of bee venom peptide.
以DL-丙交酯、乙交酯和聚乙二醇为单体,合成了DL-丙交酯/乙交酯摩尔比为6/1至15/1的可生物降解热敏聚(DL-丙交酯-共-乙交酯-b-乙二醇-b-DL-丙交酯-共-乙交酯)(PLGA-PEG-PLGA)三嵌段共聚物,并对其在体外持续释放蜂毒肽的性能进行了评估。所得共聚物在室温下可溶于水形成自由流动的流体,但在体温下会变成水凝胶。共聚物溶液的凝胶化温度会受到共聚物浓度和DL-丙交酯/乙交酯摩尔比的影响。在37℃搅拌条件下,研究了蜂毒肽从基于共聚物的水凝胶中的释放以及该水凝胶在磷酸盐缓冲液(pH 7.4)中的降解情况。蜂毒肽在体外40多天内从基于共聚物的水凝胶中释放出来,共聚物PLGA嵌段中DL-丙交酯/乙交酯摩尔比的变化对蜂毒肽的释放速率没有显著影响(P>0.05)。水凝胶在整个释放阶段经历较慢的降解,然后降解速率加快。因此,蜂毒肽的释放机制在初始阶段是菲克扩散,之后可能是扩散和降解的组合。合成的共聚物在凝胶化温度方面优于ReGel系统。这些结果表明,基于PLGA-PEG-PLGA共聚物的水凝胶可能是一种有前景的蜂毒肽持续递送平台。