Biphasic Vesicles for Topical Delivery of Interferon Alpha in Human Volunteers and Treatment of Patients with Human Papillomavirus Infections

Purpose: Topical biphasic vesicle delivery system encapsulating interferon alpha (IFN alpha) was developed as an alternative to injections used to treat human papillomavirus (HPV) infections. Methods: Biphasic lipid vesicles encapsulating increasing doses of IFN alpha (biphasic IFN alpha) were characterized for encapsulation efficiency, size, zeta potential and vesicle structure by centrifugation, dynamic light scattering, confocal microscopy and small-angle x-ray scattering. Biphasic IFN alpha delivery into human skin in vivo and topical efficacy in patients with genital warts were evaluated. Results: Average encapsulation efficiency of IFN alpha was 81-91%. The average particle size was 1000-1100 nm and zeta potential + 70 to + 78 mV. After application of 5, 15 and 40MU/g biphasic IFN alpha formulation in a topical patch on the upper inner arm in healthy volunteers, skin IFN alpha levels increased to 120 +/- 30, 380 +/- 60 and 400 +/- 80 IU/mg protein in skin homogenates (n = 5, 5, and 7), respectively. Topical application of biphasic IFN alpha (1 MU/dose) twice daily for two weeks in a pilot study with 12 patients with external condylomata acuminata resulted in a decrease in lesion size, in 2',5'-oligoadenylate synthetase activity and in tissue viral load. Conclusions: Biphasic vesicles delivered clinically significant levels of IFN alpha across intact human skin and elicited marked therapeutic effect in patients.