天津医药

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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

李雨辰1,曹岩1,王悦1,王汉杰2,李芹3,李长义1,张连云1   

  1. 1. 天津医科大学口腔医院
    2. 天津大学材料科学与工程学院纳米生物技术研究所
    3. 天津医科大学药理教研室
  • 收稿日期:2012-07-17 修回日期:2012-11-09 出版日期:2013-04-15 发布日期:2013-04-15
  • 通讯作者: 李长义

Preparation of lidocaine hydrochloride-loaded lysine modified chitosan polymeric liposomes and permeation through mouse skin in vitro

  • Received:2012-07-17 Revised:2012-11-09 Published:2013-04-15 Online:2013-04-15

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摘要： 【摘要】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）nm vs（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3.899 min，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 = 0.999 9)。LID-PLs组在5 min、10 min、30 min、2 h、4 h、6 h、8 h、12 h及24 h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10 min、30 min、1.5 h、2 h、4 h、6 h、8 h、 12 h、24 h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。

关键词: 盐酸利多卡因, 赖氨酸壳聚糖, 纳米高分子脂质体, 体外, 透皮实验

Abstract:

[Abstract] 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 lidocaine hydrochloride 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-IJ). Results  The diameter of LID-PLs was significantly smaller than that of LID-CLs (61.2±8.14 nm vs 219±7.51 nm). The specificity of HPLC was high and the standard curve equation was =0.051X-2.701，r=0.999 9. The mean cumulative permeation of lidocaine was significantly higher at 5 min,10 min, 30 min, 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-IJ 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 min, 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.

Key words: lidocaine hydrochloride, lysine modified chitosan, polymeric liposomes , in vitro, permeation through skin