盐酸利多卡因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 Polymeric Liposomes and Permeation through Mouse Skin in Vitro

目的采用赖氨酸壳聚糖十八烷基季铵盐(OQLCS)/胆固醇包载盐酸利多卡因制备纳米高分子脂质体(LID-PLs),并研究其体外透皮渗透情况。方法采用反相蒸发法制备LID-PLs和盐酸利多卡因传统脂质体(LID-CLs),用激光粒度仪/Zeta电位仪测试其粒径;建立测定盐酸利多卡因浓度的HPLC法;使用离体小鼠皮和Franz扩散池进行体外透皮实验,评价不同时间点LID-PLs、LID-CLs和盐酸利多卡因注射液(LID-IJ)的体外透皮渗透情况。结果 LID-PLs组粒径小于LID-CLs组[(61.2±8.14)nmvs(219±7.51)nm]。所建立的HPLC法专一性好,盐酸利多卡因的保留时间为3.899min,空白纳米高分子脂质体、空白透皮接收液对盐酸利多卡因的测定均无影响,其标准曲线方程为=0.051X-2.701(r=0.9999)。LID-PLs组在5min、10min、30min、2h、4h、6h、8h、12h及24h的平均累积透过量均明显高于LID-CLs组和LID-IJ组(P<0.05或P<0.01)。LID-CLs组在10min、30min、1.5h、2h、4h、6h、8h、12h、24h的平均累积透过量均明显高于LID-IJ组(P<0.05或P<0.01)。结论 LID-PLs制备简单,具有良好的透皮释放行为,所建立的HPLC方法准确可靠。

Objective To prepare the lidocaine hydrochloride-loaded lysine modified chitosan polymeric liposomes （LID-PLs） and to study its permeation characteristics through mouse skin in vitro. Methods LID-PLs and lidocaine hydrochloride-loaded conventional liposomes （LID-CLs） were prepared by reverse-phase evaporation method. The diameter and zeta potential of LID-PLs and LID-CLs were determined by dynamic light scattering （DLS） using a Brookhaven Zetasizer. A HPLC method of determination of lidoeaine hydroehloride was established. The isolated mouse skin and Franz diffusion cells were used to evaluate the permeation characteristics of LID-PLs, LID-CLs and lidocaine hydrochloride injection （LID-H）. Results The diameter of LID-PLs was significantly smaller than that of LID-CLs （61.2±8.14 nm vs 219±7.51 am）. The A specificity of HPLC was high and the standard curve equation was y=0.05 lX-2.701, r=0.999 9. The mean cumulative permeation of lidocaine was significantly higher at 5 min,10 min, 30 rain, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h after administration in LID-PLs group than those in LID-CLs group and LID-H group （P 〈 0.05 or P 〈 0.01）. The mean cumulative permeation of lidocaine was significantly higher in LID-CLs group than that in LID-IJ group at 10 rain, 30 min, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h and 24 h after administration （P 〈 0.05 or P 〈 0.01）. Conclusion The preparation of LID-PLs is simple and it has good permeation in vitro. The HPLC method is accurate and reliable.