Carafa M, Santucci E, Lucania G
Faculty of Pharmacy, University of Rome 'La Sapienza', P. le A: Moro 5, 00185, Rome, Italy.
Int J Pharm. 2002 Jan 1;231(1):21-32. doi: 10.1016/s0378-5173(01)00828-6.
Our research on topical application of lidocaine-loaded non-ionic surfactant vesicles (NSVs) was prompted by the great interest on new delivery systems for local anaesthetics. This study is focused on a novel formulation of NSVs entrapping lidocaine in the form of a free base (LID) and a hydrochloride (LIDHCl). NSVs were prepared from polyoxyethylene sorbitan monolaurate (Tween20) and cholesterol. The effect of vesicle composition and environmental pH condition (8.6-5.5) on drug encapsulation efficiency (e.e.) was investigated. Experimental strategies involved: freeze-fracture, microscopy technique, dynamic light scattering, permeation through Silastic and mouse abdominal skin, in vitro release kinetics of vesicle-entrapped drugs, fluorescence quenching analyses. Diffusion experiments showed that the flux of charged lidocaine through Silastic membrane was possible only after the vesicle encapsulation. Permeation through mouse abdominal skin of LIDHCl loaded vesicles showed a higher flux and a shorter lag time with respect to classical liposome formulations, while LID permeation rate was quite similar for NSV and liposome formulations. Vesicles were also prepared in the presence of dicetylphosphate (DCP) and N-cetylpyridinium chloride (CP) to obtain negatively and positively charged vesicles respectively, but in this case the e.e. of the drug was negligible. The possible reason of the remarkable lower e.e. observed with charged vesicles was investigated by means of fluorescence quenching experiments.
对局部麻醉药新给药系统的浓厚兴趣促使我们开展了利多卡因负载非离子表面活性剂囊泡（NSV）局部应用的研究。本研究聚焦于一种新型NSV制剂，其以游离碱（LID）和盐酸盐（LIDHCl）形式包载利多卡因。NSV由聚氧乙烯山梨醇单月桂酸酯（吐温20）和胆固醇制备而成。研究了囊泡组成和环境pH条件（8.6 - 5.5）对药物包封率（e.e.）的影响。实验策略包括：冷冻断裂、显微镜技术、动态光散射、通过硅橡胶和小鼠腹部皮肤的渗透、囊泡包载药物的体外释放动力学、荧光猝灭分析。扩散实验表明，只有在囊泡包封后，带电利多卡因才能通过硅橡胶膜。与传统脂质体制剂相比，负载LIDHCl的囊泡通过小鼠腹部皮肤的渗透通量更高，滞后时间更短，而NSV和脂质体制剂的LID渗透速率相当。还分别在磷酸二鲸蜡酯（DCP）和十六烷基氯化吡啶（CP）存在的情况下制备囊泡，以分别获得带负电和带正电的囊泡，但在这种情况下，药物的e.e.可忽略不计。通过荧光猝灭实验研究了带电荷囊泡观察到的显著较低e.e.的可能原因。
