West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
J Biomed Mater Res A. 2010 Apr;93(1):219-26. doi: 10.1002/jbm.a.32546.
In this article, we demonstrated a novel injectable polymer matrix: honokiol (HK) loaded poly (epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel for the drug local delivery. First, HK, as a model hydrophobic drug, was loaded into PCL-PEG-PCL nanoparticles by emulsion solvent evaporation method to overcome its poor water solubility. Then, the HK-loaded PCEC nanoparticles (HK-PCEC) were incorporated into thermosensitive PEG-PCL-PEG hydrogel, which was sol at low temperature and could gel as a depot for sustained release of drug in situ after topical injection. The HK-PCEC incorporated PECE hydrogel (HK-PCEC-PECE) was biodegradable and could be gradually eliminated from the injection site in about 2 weeks after subcutaneously injected into mice. The in vitro release studies indicated that HK could be released from HK-PCEC and HK-PCEC-PECE in a sustained manner. Such biodegradable smart drug-delivery system might have great potential application in injectable hydrophobic drug local delivery system.
在本文中，我们展示了一种新型的可注射聚合物基质：将荜澄茄素（HK）负载于聚（ε-己内酯）-聚（乙二醇）-聚（ε-己内酯）（PCL-PEG-PCL，PCEC）纳米粒子中，用于热敏性聚（乙二醇）-聚（ε-己内酯）-聚（乙二醇）（PEG-PCL-PEG，PECE）水凝胶中的药物局部递送。首先，将 HK 作为模型疏水性药物，通过乳液溶剂蒸发法负载到 PCL-PEG-PCL 纳米粒子中，以克服其较差的水溶性。然后，将负载 HK 的 PCEC 纳米粒子（HK-PCEC）掺入热敏性 PEG-PCL-PEG 水凝胶中，该水凝胶在低温下呈溶胶状态，经皮注射后可原位凝胶作为药物的储库，实现药物的持续释放。负载 HK 的 PCEC 掺入的 PECE 水凝胶（HK-PCEC-PECE）可生物降解，并可在皮下注射入小鼠约 2 周后从注射部位逐渐消除。体外释放研究表明，HK 可以从 HK-PCEC 和 HK-PCEC-PECE 中以持续的方式释放。这种可生物降解的智能药物递送系统在可注射疏水性药物局部递送系统中具有很大的潜在应用价值。
