Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.
Laboratory of Biomembranes, Department of Science and Technology, Structure Biology and Biotechnology Group, National University of Quilmes, IMBICE-CONICET, Bernal, Buenos Aires, Argentina.
J Pharm Sci. 2018 Sep;107(9):2411-2419. doi: 10.1016/j.xphs.2018.05.010. Epub 2018 May 24.
Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.
局部麻醉剂的给药是术后镇痛中最有效的止痛技术之一。然而，麻醉剂很容易扩散到注射部位，从而限制了麻醉时间。延长麻醉时间的一种方法是将局部麻醉剂包封在纳米结构载体（例如脂质体）中。在这里，我们报告说，使用硫酸铵梯度是提高二丁卡因（DBC）包封率（62.6%）到脂质体中的最佳策略。光散射和纳米跟踪分析用于表征囊泡的性质，例如大小、多分散性、Zeta 电位和数量。体外动力学实验表明 DBC 从脂质体中持续释放（7 小时内释放 50%）。此外，体外（培养的 3T3 细胞）和体内（斑马鱼）毒性试验表明，离子梯度脂质体能够降低 DBC 的细胞/心脏毒性，并减少斑马鱼幼虫的形态变化。此外，在小鼠中经浸润给药后，包封的 DBC（27 小时）的麻醉时间长于游离 DBC（11 小时），在 320 μM（0.012%）时，证实其是一种有前途的长效脂质体制剂，可用于 DBC 的注射给药。
