title: In vivo sustained dermal delivery and pharmacokinetics of interferon alpha in biphasic vesicles after topical application.
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 (1g, 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 cm(2)) of IFN α within 6h 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 6h. 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.
authors.affiliation: Helix BioPharma Corp., Saskatoon, SK, Canada S7N 3R2.
authors.forename: Martin
authors.initials: M
authors.lastname: King
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Deborah
authors.initials: D
authors.lastname: Michel
authors.forename: Ravinderjit
authors.initials: R
authors.lastname: Batta
authors.forename: Marianna
authors.initials: M
authors.lastname: Foldvari
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001835:Body Weight; D002417:Cattle; D002460:Cell Line; D016503:Drug Delivery Systems; D006168:Guinea Pigs; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008055:Lipids / Q000737:chemistry; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000188:drug therapy*; D010743:Phospholipids / Q000737:chemistry; D012867:Skin / Q000187:drug effects; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D008055:Lipids; D010743:Phospholipids