文献：An efficient and long-acting local anesthetic: ropivacaine-loaded lipid-polymer hybrid nanoparticles for the control of pain

文献链接：https://pubmed.ncbi.nlm.nih.gov/30774342/

作者：Aimei Li , Feng Yang2,Jiaying Xin, Xuebo Bai

相关产品：PCL

原文摘要：

Purpose: Local anesthetics are used clinically for the control of pain following operation (including gastrointestinal surgery) or for the management of other acute and chronic pain. This study aimed to develop a kind of lipid-polymer hybrid nanoparticles (LPNs), which were constructed using poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) as the hydrophilic lipid shell and poly-ε-caprolactone (PCL) as the hydrophobic polymeric core.

Methods: Ropivacaine (RPV) was entrapped in the LPNs (RPV-LPNs) and the physicochemical and biochemical properties such as size, zeta potential, drug release, and cytotoxicity were studied. The long-lasting effects and safety aspects of the LPNs were evaluated in vitro and in vivo.

Results: The particle size and zeta potential of RPV-LPNs were 112.3±2.6 nm and -33.2±3.2 mV,

with an entrapment efficiency (EE) of 90.2%±3.7%. Ex vivo permeation efficiency of LPNs was better than the drug solution. The RPV-LPNs exhibited a long-lasting in vivo anesthesia effect in both rats and mice.

Conclusion: Considering the low cytotoxicity, the LPNs prepared here could be used as an

efficient local anesthetic for the control of pain.

PCL，即聚己内酯，是一种有机高分子聚合物。它是以二元醇为引发剂，由己内酯开环聚合而得到的热塑性结晶聚酯。PCL是一种白色不透明固体，具有一定刚性和强度，表现为典型的树脂特性。它易溶于甲苯、四氢呋喃、乙酸乙酯和二氯甲烷等溶剂中，易成膜。PCL还具有良好的生物降解性、生物相容性和无有害性，这些特性使得PCL被用作医用生物降解材料及药物控制释放体系。PCL的应用较广，例如PCL在脂质聚合物杂化纳米粒子LPNs制备中有多重应用。

图为：RPV-lpn的组成和示意图

PCL在LPNs制备中的应用：

PCL作为聚合物，PEG-DSPE作为脂质，卵磷脂作为亲脂性表面活性剂溶解在丙酮作为有机溶剂中形成油相。将RPV溶解于十二烷基硫酸钠溶液中，形成内部水相。接下来，将溶液在冰洗溶液中超声进行乳化。将合成的纳米乳液倒入多®F-127溶液中，并在冰浴中再次超声。然后在室温下搅拌混合物过夜，蒸发掉有机溶剂，收集合成离心的RPV-LPNs，用超纯水洗涤，冻干获得自由流动的粉末。LPNs（E-LPNs）采用相同的方法制备，不存在RPV。

图为：lpn的体外药物释放行为和溶液被描述为累积RPV释放（%）与时间的关系

结论：本研究以PEG-DSPE为亲水脂壳，PCL为疏水聚合物核。RPV-LPNs体积小，PDI较窄，药物包封效率高，细胞有害性低。LPNs的体外渗透效率优于药物溶液。lpn的持续释放行为效果一致，lpn可作为一种长效局anaesthetic。