Guo J, Ping Q, Sun G, Jiao C
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
Int J Pharm. 2000 Jan 25;194(2):201-7. doi: 10.1016/s0378-5173(99)00361-0.
Two kinds of vesicles with and without the presence of sodium cholate (flexible vesicles and conventional vesicles) were prepared, using cyclosporin A as model drug. When applied onto the excised abdominal skin of mice non-occlusively, the enhancing effects of vesicles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. The effect of sodium cholate micelles was also studied. In vivo study was carried out by topical application of vesicles onto the mice skin and drug serum concentration was detected. Results showed that after 8 h of administration, flexible vesicles transported 1.16 microg of cyclosporin A through per cm(2) mice skin and amounted to 1.88 microg 24 h later. The residual amount in the skin was 1.78+/-0.51 microg/cm(2). However, flexible vesicles failed to transport measurable amount of drug through pre-hydrated skin while deposited 2.39+/-0.26 microg/cm(2) into the skin. Conventional vesicles failed to transfer cyclosporin A into the receiver while accumulated 0. 72+/-0.19 microg/cm(2) of drug in the skin. Furthermore, 1 and 40% sodium cholate micelles precluded the transport of cyclosporin A. In vivo studies indicated that with the application of flexible vesicles, serum drug concentration of 53.43+/-9.24 ng/ml was detected 2 h later. After the stratum corneum of mouse skin has been destroyed by shaving, flexible vesicles transferred large amount of drug into blood, up to 187.32+/-53.21 ng/ml after 1 h of application. Conventional vesicles failed to deliver measurable amount of drug into the blood under normal skin condition. In conclusion, flexible vesicle is better than conventional vesicle as the carrier for transdermal delivery of cyclosporin A. Penetration and fusion have been suggested to be two major functional mechanisms. Hydration is detrimental to the enhancement effect. Stratum corneum constitutes main barrier to the transport of lipophilic cyclosporin A.
以环孢素A为模型药物，制备了两种分别含有和不含胆酸钠的囊泡（柔性囊泡和传统囊泡）。采用体外渗透技术，在非封闭条件下将其应用于小鼠离体腹部皮肤，评估囊泡对环孢素A渗透的增强作用。同时研究了胆酸钠胶束的作用。通过将囊泡局部应用于小鼠皮肤进行体内研究，并检测药物血清浓度。结果显示，给药8小时后，柔性囊泡每平方厘米小鼠皮肤转运了1.16微克环孢素A，24小时后达到1.88微克。皮肤中的残留量为1.78±0.51微克/平方厘米。然而，柔性囊泡在预水化皮肤上未能转运可测量量的药物，而是在皮肤中沉积了2.39±0.26微克/平方厘米。传统囊泡未能将环孢素A转移到接收液中，而是在皮肤中积累了0.72±0.19微克/平方厘米的药物。此外，1%和40%的胆酸钠胶束阻碍了环孢素A的转运。体内研究表明，应用柔性囊泡后，2小时后检测到血清药物浓度为53.43±9.24纳克/毫升。在剃除小鼠皮肤角质层后，柔性囊泡将大量药物转移到血液中，给药1小时后高达187.32±53.21纳克/毫升。在正常皮肤条件下，传统囊泡未能将可测量量的药物输送到血液中。总之，作为环孢素A透皮给药的载体，柔性囊泡优于传统囊泡。渗透和融合被认为是两个主要的功能机制。水化对增强作用不利。角质层是亲脂性环孢素A转运的主要屏障。
