Jain Subheet, Tiwary Ashok K, Sapra Bharti, Jain Narendra K
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Patiala [Punjab] 147 002 India.
AAPS PharmSciTech. 2007 Dec 21;8(4):E111. doi: 10.1208/pt0804111.
The purpose of the present research was to investigate the mechanism for improved intercellular and intracellular drug delivery from ethosomes using visualization techniques and cell line study. Ethosomal formulations were prepared using lamivudine as model drug and characterized in vitro, ex vivo and in vivo. Transmission electron microscopy, scanning electron microscopy, and fluorescence microscopy were employed to determine the effect of ethosome on ultrastructure of skin. Cytotoxicity and cellular uptake of ethosome were determined using T-lymphoid cell line (MT-2). The optimized ethosomal formulation showed 25 times higher transdermal flux (68.4 +/- 3.5 microg/cm(2)/h) across the rat skin as compared with that of lamivudine solution (2.8 +/- 0.2 microg/cm(2)/h). Microscopic studies revealed that ethosomes influenced the ultrastructure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular region of deeper skin layers. Results of cellular uptake study showed significantly higher intracellular uptake of ethosomes (85.7% +/- 4.5%) as compared with drug solution (24.9% +/- 1.9%). The results of the characterization studies indicate that lipid perturbation along with elasticity of ethosomes vesicles seems to be the main contributor for improved skin permeation.
本研究的目的是使用可视化技术和细胞系研究来探究乙醇脂质体改善细胞间和细胞内药物递送的机制。以拉米夫定为模型药物制备乙醇脂质体制剂，并进行体外、离体和体内表征。采用透射电子显微镜、扫描电子显微镜和荧光显微镜来确定乙醇脂质体对皮肤超微结构的影响。使用T淋巴细胞系（MT-2）测定乙醇脂质体的细胞毒性和细胞摄取。优化后的乙醇脂质体制剂经大鼠皮肤的透皮通量（68.4±3.5μg/cm²/h）比拉米夫定溶液（2.8±0.2μg/cm²/h）高25倍。显微镜研究表明，乙醇脂质体影响角质层的超微结构。在较深层皮肤的细胞间区域观察到来自囊泡的层状堆积的不同区域。细胞摄取研究结果显示，与药物溶液（24.9%±1.9%）相比，乙醇脂质体的细胞内摄取显著更高（85.7%±4.5%）。表征研究结果表明，脂质扰动以及乙醇脂质体囊泡的弹性似乎是改善皮肤渗透的主要因素。
