Qiao Mingxi, Chen Dawei, Hao Tangna, Zhao Xiuli, Hu Haiyang, Ma Xichen
School of Pharmacy, P.O. Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, PR China.
Int J Pharm. 2007 Dec 10;345(1-2):116-24. doi: 10.1016/j.ijpharm.2007.05.056. Epub 2007 May 31.
The objectives of this study were to investigate the potential interactions between the model protein drug (bee venom peptide, BVP) and thermosensitive poly(dl-lactide-co-glycolide-b-ethyleneglycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymers and to examine the drug-copolymer interactions on the in vitro drug release and hydrogel degradation. The PLGA-PEG-PLGA copolymers were synthesized by ring-opening copolymerization of dl-lactide and glycolide with PEG as an initiator. Drug-copolymer co-precipitate blends were prepared and analyzed by Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) to characterize the specific interactions between drug and copolymer. For the better understanding the drug-copolymer interactions on drug release, insulin was selected for comparison. The release of the two protein drugs from the copolymer-based hydrogels and hydrogel degradation was studied at 37 degrees C under agitation. The results of FTIR and XRD indicated that the hydrogen bonding interactions existed between the NH group of BVP and CO group of the copolymers. The insulin and BVP released from the copolymer hydrogel over 15 and 40 days, respectively. The BVP-copolymer interactions retarded the BVP release rate and degradation of hydrogel, but did not significantly affect the biological activity of BVP. These results indicate that the drug-copolymer interactions need to be considered when attempting to use PLGA-PEG-PLGA hydrogels as sustained delivery carriers of protein or peptide drugs.
本研究的目的是研究模型蛋白药物（蜂毒肽，BVP）与热敏聚（聚（d，l-丙交酯-共-乙交酯-b-乙二醇-b-d，l-丙交酯-共-乙交酯））（PLGA-PEG-PLGA）共聚物之间的潜在相互作用，并研究药物-共聚物相互作用对体外药物释放和水凝胶降解的影响。PLGA-PEG-PLGA共聚物是通过以PEG为引发剂，使d，l-丙交酯和乙交酯进行开环共聚反应合成的。制备了药物-共聚物共沉淀混合物，并通过傅里叶变换红外（FTIR）光谱和X射线衍射（XRD）进行分析，以表征药物与共聚物之间的特定相互作用。为了更好地理解药物-共聚物相互作用对药物释放的影响，选择胰岛素进行比较。在37℃搅拌条件下研究了两种蛋白药物从基于共聚物的水凝胶中的释放以及水凝胶的降解。FTIR和XRD结果表明，BVP的NH基团与共聚物的CO基团之间存在氢键相互作用。胰岛素和BVP分别在15天和40天内从共聚物水凝胶中释放出来。BVP-共聚物相互作用延缓了BVP的释放速率和水凝胶的降解，但对BVP的生物活性没有显著影响。这些结果表明，在尝试将PLGA-PEG-PLGA水凝胶用作蛋白质或肽药物的持续递送载体时，需要考虑药物-共聚物相互作用。
