In vivo sustained dermal delivery and pharmacokinetics of interferon alpha in biphasic vesicles after topical application

Eur J Pharm Biopharm. 2013 Aug;84(3):532-9. doi: 10.1016/j.ejpb.2013.01.014. Epub 2013 Mar 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacokinetics*
  • Body Weight
  • Cattle
  • Cell Line
  • Drug Delivery Systems*
  • Guinea Pigs
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / pharmacokinetics*
  • Lipids / chemistry
  • Papillomaviridae
  • Papillomavirus Infections / drug therapy*
  • Phospholipids / chemistry
  • Skin / drug effects
  • Time Factors

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Lipids
  • Phospholipids