In vivo sustained dermal delivery and pharmacokinetics of interferon alpha in biphasic vesicles after topical application |
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| Institution: | 1. Helix BioPharma Corp., Saskatoon, SK, Canada S7N 3R2;2. University of Waterloo, School of Pharmacy, Waterloo, Canada N2L 3G1;1. University of Chicago, Department of Medicine, Section of Gastroenterology, Chicago, IL, United States;2. University of Chicago, Department of Human Genetics, Chicago, IL, United States;1. Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut, USA;2. Department of Pediatrics, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA;3. Department of Pediatrics, Division of Pediatric Nephrology, McGill University Health Centre, Montreal, Quebec, Canada;4. Department of Biostatistics, University of Washington, Seattle, Washington, USA;5. Nephrology and Hypertension, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio, USA;6. Division of General Internal Medicine, Veterans Administration Medical Center, University of California, San Francisco, California, USA;7. Department of Internal Medicine, Section of Nephrology, Mount Sinai School of Medicine, New York, New York, USA;8. Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut and VA Medical Center, West Haven, Connecticut, USA;1. Vin?a Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia;2. Faculty of Civil Engineering, University of Belgrade, Bulevar Kralja Aleksandra 73, 11000 Belgrade, Serbia;3. ICTM-Institute of Electrochemistry, University of Belgrade, Njego?eva 12, 11001 Belgrade, Serbia;4. Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11000 Belgrade, Serbia;1. Department of Medical Microbiology and Parasitology, School of Pharmacy, University of Barcelona, Joan XXIII Ave., 08028 Barcelona, Spain;2. Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Barcelona, Joan XXIII Ave., 08028 Barcelona, Spain;3. Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, Campus of Cartuja St., 18071 Granada, Spain;1. Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, China;2. Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, China;3. Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, 250012, China |
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| Abstract: | Biphasic vesicles, a novel nanostructured lipid-based delivery system show potential for topical application of interferon alpha (IFN α) for the treatment of human papillomavirus (HPV) infections (anogenital warts). Dermal delivery of IFN α encapsulated in biphasic vesicles (BPV-IFN α), applied topically to the skin, was characterized in a guinea pig model.BPV-IFN α (1 g, 2 MIU/g) was topically applied either as a single or multiple treatments on the skin of guinea pigs. As a comparison with currently used regimens, IFN α solution was administered intravenously or intradermally. Skin and serum samples were collected over 96 h, IFN α levels were determined by an antiviral assay, and half-life (t1/2) and elimination (k) rates were calculated.Topical BPV-IFN α treatment resulted in maximum skin levels (about 100,000 U/100 cm2) of IFN α within 6 h and maintained for 72–96 h. Clearance from the skin after intradermal injections was initially fast (t1/2 0.62 h, k 1.1179 h?1), followed by a slower steady decrease after 6 h. After intravenous and intradermal administration, IFN α was rapidly cleared from the serum, t1/2 0.75 h, k 0.9271 h?1 and t1/2 1.28 h, k 0.5421 h?1, respectively, whereas after topical application, IFN α levels remained below 100 U/mL. Topical application of BPV- IFN α resulted in sustained delivery of biologically active IFN α locally into skin with minimal systemic exposure. |
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