穿膜肽纳米类脂质体包载利多卡因的透皮特性及表面麻醉效果初探

Preliminary study on transdermal characteristics and sunface anesthetic effects of lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome in animals

目的 研究穿膜肽纳米类脂质体包载利多卡因（lidocaine hydrochloride loaded transactivator of transcription peptide conjugated nano-niosome,LID-TAT-N）在动物体内外透皮情况及其表面麻醉效果,为研制新型口腔表面麻醉剂提供依据.方法 制备LID-TAT-N,传统脂质体包载利多卡因（lidocaine hydrochloride loaded conventional liposome,LID-CL）,分别检测粒径、电势和包封率.用离体小鼠皮进行12h体外透皮实验,测定并比较LID-TAT-N组、LID-CL组、利多卡因注射液（LID injection,LID-IJ）组（每组样本量为6）单位面积累计透过量;通过兔角膜反射比较LID-TAT-N组、LID-CL组和LID-IJ组（每组样本量为6）表面麻醉效果.结果 LID-TAT-N组脂质体粒径[（152.7±10.6） nm]显著小于LID-CL组[（259.5±15.5） nm,P＜0.01].LID-TAT-N组12 h单位面积累计透过量达（1 340.0±97.5） μg＆#183;cm-2,显著高于LID-CL组[（1 060.6±80.2） μg＆#183;cm-2]和LID-IJ组[（282.6±65.1）μg＆#183;cm-2]（p＜0.05）.LID-TAT-N组具有表面麻醉效果,其麻醉持续时间[（24.8±2.8） min]显著长于LID-IJ组[（14.5±2.3） min,P＜0.05],与LID-CL组[（21.3±5.6）min]差异无统计学意义（P＞0.05）.结论 LID-TAT-N具有良好的透皮能力,有表面麻醉效果.

Objective To prepare a new dental topical anesthetics,lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome（LID-TAT-N）,and to evaluate its transdermal properties and topical anesthesia effects.Methods LID-TAT-N was prepared using reversephase evaporation method,and lidocaine loaded conventional liposome（LID-CL） was prepared in the same manner as positive control.The diameter,ξ potential and encapsulation efficiency of LID-TAT-N and LID-CL were measured.The skin permeation of LID-TAT-N was examined,and compared with LID-CL and lidocaine injection（LID-IJ,as negative control）,using a Franz diffusion cell mounted with depilated mouse skin in vitro for 12 hours.Each experiment was repeated six times.The anesthetic effect of the new topical anesthetic was investigated on the cornea of rabbits.Results The mean diameter of LID-TAT-N was smaller than that of LID-CL[（152.7 ± 10.6） nm vs.（259.5 ± 15.5） nm,P〈0.01].The 12 h cumulative permeation amount was significantly higher in LID-TAT-N group[（1 340.0±97.5） μg＆#183; cm-2] than those of LID-CL and LID-IJ groups[（1 060.6±80.2）,（282.6±65.1） μg＆#183; cm-2,respectively,P〈0.05].Rabbit corneal reflex results showed that LID-TAT-N had anesthetic effect and the duration of analgesia[（24.8±2.8） min] was also longer than that of LID-IJ[（14.5 ± 2.3） min,P〈0.05].Conclusions LID-TAT-N had good transdermal ability,and the advanced skin penetration feature can improve its tropical anesthetic effect.