Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas - Unicamp, P.O. Box - 6109, CEP, Campinas, SP, 13083-862, Brazil.
Department of Biophysics, Federal University of São Paulo - UNIFESP, São Paulo, São Paulo, Brazil.
Pharm Res. 2018 Oct 10;35(12):229. doi: 10.1007/s11095-018-2512-4.
Etidocaine (EDC) is a long lasting local anesthetic, which alleged toxicity has restricted its clinical use. Liposomes can prolong the analgesia time and reduce the toxicity of local anesthetics. Ionic gradient liposomes (IGL) have been proposed to increase the upload and prolong the drug release, from liposomes.
First, a HPLC method for EDC quantification was validated. Then, large unilamellar vesicles composed of hydrogenated soy phosphatidylcholine:cholesterol with 250 mM (NH)SO - inside gradient - were prepared for the encapsulation of 0.5% EDC. Dynamic light scattering, nanotracking analysis, transmission electron microscopy and electron paramagnetic resonance were used to characterize: nanoparticles size, polydispersity, zeta potential, concentration, morphology and membrane fluidity. Release kinetics and in vitro cytotoxicity tests were also performed.
IGL showed average diameters of 172.3 ± 2.6 nm, low PDI (0.12 ± 0.01), mean particle concentration of 6.3 ± 0.5 × 10/mL and negative zeta values (-10.2 ± 0.4 mV); parameters that remain stable during storage at 4°C. The formulation, with 40% encapsulation efficiency, induced the sustained release of EDC (ca. 24 h), while reducing its toxicity to human fibroblasts.
A novel formulation is proposed for etidocaine that promotes sustained release and reduces its cytotoxicity. IGL can come to be a tool to reintroduce etidocaine in clinical use.
依替卡因（EDC）是一种长效局麻药，但其毒性限制了其临床应用。脂质体可以延长镇痛时间并降低局麻药的毒性。有人提出离子梯度脂质体（IGL）可以增加药物摄取并延长药物释放时间。
首先，验证了用于 ED C 定量的 HPLC 方法。然后，用氢化大豆磷脂酰胆碱：胆固醇（250 mM（NH）SO - ）制备大单层囊泡，用于包封 0.5%的 EDC。动态光散射、纳米跟踪分析、透射电子显微镜和电子顺磁共振用于表征：纳米颗粒的大小、多分散性、Zeta 电位、浓度、形态和膜流动性。还进行了释放动力学和体外细胞毒性试验。
IGL 平均直径为 172.3 ± 2.6nm，PDI 低（0.12 ± 0.01），平均粒径浓度为 6.3 ± 0.5×10/ml，Zeta 值为负（-10.2 ± 0.4 mV）；这些参数在 4°C 下储存时保持稳定。该制剂的包封效率为 40%，可诱导 EDC 持续释放（约 24 小时），同时降低其对人成纤维细胞的毒性。
提出了一种新的依替卡因制剂，可促进其持续释放并降低其细胞毒性。IGL 可以成为重新引入依替卡因临床应用的工具。
