Liposome encapsulated prostaglandin E 1 in erectile dysfunction: correlation between in vitro delivery through foreskin and efficacy in patients

Abstract

Objectives. To test the delivery of prostaglandin E 1 (PGE 1) in novel transdermal liposomal formulations through foreskin and to determine whether there is a correlation between in vitro transdermal absorption and in vivo efficacy in patients with erectile dysfunction. Methods. The in vitro transdermal absorption of PGE 1 through excised foreskin from liposomal formulations was tested in diffusion cells using radiolabeled drug. The in vivo studies were carried out on 5 patients (aged 54 to 70 years) in a double-blind, placebo-controlled fashion. The patients were treated topically on the penis with three different active formulations containing 0.05% PGE 1 and a placebo at least 1 week apart. The change in systolic peak flow velocities in the cavernosal arteries after treatment was monitored by duplex color Doppler ultrasonography with spectral analysis every 15 minutes for 1 hour. Results. The permeability coefficient (Kp) of PGE 1 from the three liposomal formulations tested was found to be 0.10, 1.66, and 3.82 × 10 −4 cm/hr, respectively. Peak systolic flow velocities in the deep cavernosal arteries of patients increased significantly compared with preapplication values (0.05 < P ≤ 0.1) after application of two of the transdermal liposomal PGE 1 formulations tested (the two with the highest Kp). The highest mean peak systolic flow velocity was achieved at 45 minutes after application of the formulations. The most effective formulation in this study resulted in a sevenfold increase in mean flow velocity compared with baseline values. Conclusions. Topical application of PGE 1 in a novel transdermal liposomal delivery system can enhance penetration of the drug into the deep cavernosal bodies and increase peak systolic flow velocities in patients with erectile dysfunction. The transdermal flux and permeability of PGE 1 measured in vitro correlate well with the color Doppler ultrasound results in patients. The efficacy of a formulation in the development process may be predicted from in vitro absorption studies.