盐酸利多卡因跨膜肽纳米高分子脂质体的制备与体外透皮实验研究

Preparation of Lidocaine Hydrochloride-Loaded Transactivation Transcriptional Activator Conjugated Polymeric Liposomes and Its in Vitro Skin Permeation in Mice

目的采用赖氨酸壳聚糖十八烷基季铵盐(OQLCS)组装跨膜肽(TAT)包载盐酸利多卡因制备纳米高分子脂质体,并研究其体外透皮渗透情况。方法采用反相蒸发法制备盐酸利多卡因跨膜肽纳米高分子脂质体(LID-TAT-PLs),使用离体小鼠皮和Franz扩散池进行体外透皮实验,HPLC法测定接收液中盐酸利多卡因的浓度,评价LID-TAT-PLs、未组装跨膜肽的盐酸利多卡因纳米高分子脂质体(LID-PLs)和盐酸利多卡因注射液(LID-IJ)的体外透皮渗透情况。结果 LID-TAT-PLs的体外透皮速度和累积透过量均明显高于LID-PLs和LID-IJ。LID-TAT-PLs组的24h累积透过量达(88.15±11.11)%,明显高于LID-PLs的(73.91±12.13)%和LID-IJ的(26.31±5.43)%,差异有统计学意义(P<0.05)。结论 TAT可以明显促进药物的透皮渗透,LID-TAT-PLs制备简单,具有良好的透皮释放行为。

Objective To prepare the lidocaine hydrochloride-loaded transactivation （TAT） conjugated octadecyl quaternized lysine modified chitosan polymeric liposomes （LID-TAT-PLs） and to study its in vitro skin permeation characters in mice. Methods LID-TAT-PLs were prepared by reverse-phase evaporation method. The concentrations of lidocaine hy- drochloride were determined by HPLC. The isolated mouse skin and Franz diffusion cell were used to evaluate the characters of permeation of LID-TAT-PLs, LID-PLs and lidocaine hydrochloride injection （LID-IJ）. Results The permeation rate and cumulative permeation amount were significantly higher in LID-TAT-PLs group than those of LID-PLs and LID-IJ groups （P〈 0.05）. Conclusion TAT can significantly enhance the transdermal permeation of drugs in mice. The LID-TAT-PLs can be prepared via a relatively simple method.