Foldvari M, Oguejiofor C J, Wilson T W, Afridi S K, Kudel T A
College of Pharmacy and Nutrition and Departments of Pharmacology, Surgery, and Medical Imaging, University of Saskatchewan, Saskatoon, SK, Canada S7N 5C9.
J Pharm Sci. 1998 Jun;87(6):721-5. doi: 10.1021/js970425s.
The aim of this study was to assess the rate and extent of transcutaneous delivery of prostaglandin E1 (PGE1) from various formulations [liposomal, novel biphasic, and nonliposomal (oil/water cream) delivery systems] in vitro using diffusion cells and in vivo using laser doppler flowmetry, to aid in the development of a topically active preparation for the treatment of male sexual dysfunction. Percutaneous absorption through adult human foreskin was tested in flow-through diffusion cells using [3H]PGE1. Nine healthy volunteers participated in the crossover, randomized, double-blind, placebo-controlled study, where 0.1 g of each preparation was applied to a 4 cm2 area on the forearm. Laserflo BPM2 blood perfusion monitor with Model P-430 skin probe was used for evaluating skin blood perfusion. Encapsulation of PGE1 into novel biphasic delivery systems resulted in significantly increased skin blood perfusion relative to traditional liposomal, nonliposomal, and placebo formulations (6.25 +/- 1.58 vs 2.72 +/- 0.79, 0.53 +/- 0.64, and 0.58 +/- 0.06 mLLD/min/100 g, respectively, n = 9). The in vitro absorption of PGE1 through foreskin correlated well with the in vivo data (respective permeability coefficients 3.33, 1.57, and 1. 40 x 10(-4) cm/h). Formulation parameters greatly influence the absorption of PGE1 through skin as measured by laser doppler flowmetry, but by the application of a novel topical delivery technology, a significant enhancement of PGE1 delivery can be achieved.
本研究的目的是使用扩散池在体外以及使用激光多普勒血流仪在体内评估前列腺素E1（PGE1）从各种制剂[脂质体、新型双相和非脂质体（油/水乳剂）递送系统]经皮递送的速率和程度，以帮助开发一种用于治疗男性性功能障碍的局部活性制剂。使用[3H]PGE1在流通扩散池中测试PGE1透过成人人类包皮的经皮吸收。九名健康志愿者参与了交叉、随机、双盲、安慰剂对照研究，其中将0.1 g每种制剂涂抹在前臂上4 cm2的区域。使用带有P-430皮肤探头的Laserflo BPM2血液灌注监测仪评估皮肤血液灌注。相对于传统脂质体、非脂质体和安慰剂制剂，将PGE1封装到新型双相递送系统中可显著增加皮肤血液灌注（分别为6.25±1.58 vs 2.72±0.79、0.53±0.64和0.58±0.06 mLLD/min/100 g，n = 9）。PGE1透过包皮的体外吸收与体内数据相关性良好（各自的渗透系数为3.33、1.57和1.40×10(-4) cm/h）。通过激光多普勒血流仪测量，制剂参数极大地影响PGE1透过皮肤的吸收，但通过应用新型局部递送技术，可以实现PGE1递送的显著增强。
