Shanmugam Srinivasan, Song Chung-Kil, Nagayya-Sriraman Santhoshkumar, Baskaran Rengarajan, Yong Chul-Soon, Choi Han-Gon, Kim Dae-Duk, Woo Jong Soo, Yoo Bong-Kyu
College of Pharmacy, Yeungnam University, Kyungsan, 712-749, Korea.
Arch Pharm Res. 2009 Jul;32(7):1067-75. doi: 10.1007/s12272-009-1713-0. Epub 2009 Jul 31.
This study was undertaken to evaluate the physicochemical properties and skin permeation of liposome formulations containing clindamycin phosphate (CP), especially when charge was imparted to the liposome. Five different liposome formulations were prepared using Phospholipon 85G (PL) and cholesterol (CH) by conventional lipid film hydration technique. Molar ratio of CH to PL was varied in the range of 0.16-1.0. Charged liposomes were prepared in the same way with addition of 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA) as charge carrier lipid for cationic or anionic charge of the liposome, respectively. Fresh full-thickness mice skin was taken and used for skin permeation study using Keshary-Chien diffusion cell with 1.77 cm(2) diffusion area at 37 degrees C. All liposome formulations prepared showed homogeneous size distribution with mean particle size of about 1 mum or less. Among the five liposome formulations prepared, formulation with the molar ratio of 0.5 showed the best result in the physicochemical properties such as polydispersity index, entrapment efficiency, size evolution, and ability of the liposome to retain CP as of entrapped in the vesicles. Charge-impartation of the formulation with cationic charge carrier lipid resulted in additional benefit in terms of inhibition of size evolution, the ability of the liposome to retain CP in the vesicles, and skin permeation. Steady state flux of the drug through the mice skin in the cationic liposome vesicles was 0.75 +/- 0.01 microg/cm(2)h while that in the control (dissolved into mixed alcohol solution) was 0.17 microg/cm(2)h. One half molar ratio of CH to PL was optimal in terms of physicochemical properties of the liposome formulation containing CP, and incorporation of cationic charge carrier lipid appeared to provide additional benefits for the stability of the liposome formulation and skin permeation of the drug.
本研究旨在评估含磷酸克林霉素（CP）的脂质体制剂的物理化学性质及皮肤渗透性，尤其是当脂质体带有电荷时的情况。采用常规脂质膜水化技术，使用磷脂酰胆碱85G（PL）和胆固醇（CH）制备了五种不同的脂质体制剂。CH与PL的摩尔比在0.16 - 1.0范围内变化。通过分别添加1,2 - 二油酰基 - 3 - 三甲基氯化铵盐（DOTAP）和1,2 - 二肉豆蔻酰 - sn - 甘油 - 3 - 磷酸单钠盐（DMPA）作为电荷载体脂质，以相同方式制备带正电荷或负电荷的脂质体，使脂质体分别带有阳离子或阴离子电荷。取新鲜的小鼠全层皮肤，使用扩散面积为1.77 cm²的Keshary - Chien扩散池在37℃下进行皮肤渗透研究。所制备的所有脂质体制剂均显示出均匀的粒径分布，平均粒径约为1μm或更小。在所制备的五种脂质体制剂中，摩尔比为0.5的制剂在多分散指数、包封率、粒径变化以及脂质体保留包裹在囊泡中的CP的能力等物理化学性质方面表现出最佳结果。用阳离子电荷载体脂质对制剂进行电荷赋予，在抑制粒径变化、脂质体在囊泡中保留CP的能力以及皮肤渗透性方面带来了额外的益处。阳离子脂质体囊泡中药物透过小鼠皮肤的稳态通量为0.75±0.01μg/cm²·h，而对照组（溶解于混合醇溶液中）为0.17μg/cm²·h。就含CP的脂质体制剂的物理化学性质而言，CH与PL的摩尔比为1/2时是最佳的，并且加入阳离子电荷载体脂质似乎为脂质体制剂的稳定性和药物的皮肤渗透性提供了额外的益处。
