Abstract This study describes the encapsulation of the local anaesthetic lidocaine (LDC) in large unilamellar liposomes (LUV) prepared in a scalable procedure, with hydrogenated soybean phosphatidylcholine, cholesterol and mannitol. Structural properties of the liposomes were assessed by dynamic light scattering, nanoparticle tracking analysis and transmission electron microscopy. A modified, two-compartment Franz-cell system was used to evaluate the release kinetics of LDC from the liposomes. The in vivo anaesthetic effect of liposomal LDC 2% (LUVLDC) was compared to LDC 2% solution without (LDCPLAIN) or with the vasoconstrictor epinephrine (1:100 000) (LDCVASO), in rat infraorbital nerve blockade model. The structural characterization revealed liposomes with spherical shape, average size distribution of 250 nm and low polydispersity even after LDC incorporation. Zeta potential laid around –30 mV and the number of suspended liposomal particles was in the range of 1012 vesicles/mL. Also the addition of cryoprotectant (mannitol) did not provoke structural changes in liposomes properties. In vitro release profile of LDC from LUV fits well with a biexponential model, in which the LDC encapsulated (EE% = 24%) was responsible for an increase of 67% in the release time in relation to LDCPLAIN (p < 0.05). Also, the liposomal formulation prolonged the sensorial nervous blockade duration (∼70 min), in comparison with LDCPLAIN (45 min), but less than LDCVASO (130 min). In this context, this study showed that the liposomal formulations prepared by scalable procedure were suitable to promote longer and safer buccal anaesthesia, avoiding side effects of the use of vasoconstrictors.

中文翻译：

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用于改善浸润性颊麻醉的基于脂质体的利多卡因制剂

摘要 本研究描述了将局部麻醉剂利多卡因 (LDC) 封装在以可扩展程序制备的大型单层脂质体 (LUV) 中，其中包含氢化大豆磷脂酰胆碱、胆固醇和甘露醇。通过动态光散射、纳米粒子跟踪分析和透射电子显微镜评估脂质体的结构特性。改良的两室 Franz 细胞系统用于评估 LDC 从脂质体中的释放动力学。在大鼠眶下神经阻滞模型中，将脂质体 LDC 2% (LUVLDC) 的体内麻醉效果与不含 (LDCPLAIN) 或含有血管收缩剂肾上腺素 (1:100 000) (LDCVASO) 的 LDC 2% 溶液进行比较。结构表征表明脂质体呈球形，250 nm 的平均尺寸分​​布和低多分散性，即使在加入 LDC 后。Zeta 电位约为 –30 mV，悬浮脂质体颗粒的数量在 1012 个囊泡/mL 的范围内。此外，添加冷冻保护剂（甘露醇）不会引起脂质体特性的结构变化。LUV 的 LDC 体外释放曲线与双指数模型非常吻合，其中封装的 LDC (EE% = 24%) 导致与 LDCPLAIN 相关的释放时间增加 67% (p < 0.05)。此外，与 LDCPLAIN（45 分钟）相比，脂质体制剂延长了感觉神经阻滞持续时间（~70 分钟），但少于 LDCVASO（130 分钟）。在此背景下，本研究表明，通过可扩展程序制备的脂质体制剂适用于促进更长时间和更安全的口腔麻醉，