title: Transcutaneous IL-2 uptake mediated by Transfersomes depends on concentration and fractionated application.
abstract: BACKGROUND
  Transfersomes (TF) are new, ultradeformable carriers with characteristics that enable them to penetrate the skin spontaneously. TFs are able to transport noninvasively both low- and high-molecular-weight molecules into the body.
  
  
  METHODS
  TFs contain phosphatidylcholine and sodium cholate. Recombinant human interleukin-2 (Proleukin, Chiron) was added to the TFs and incubated for 24 h at 4 degrees C. The immunotransfersomes (ITF) were isolated from free interleukin-2 (IL-2) by filtration (Centrisart, Sartorius). Twenty-five thousand, 50,000 and 150,000 IU pure IL-2 and ITFs, which had been incubated with the same concentrations of IL-2, were applied subcutaneously (s.c.) (n = 8) and epicutaneously (e.c.) (n = 8) to mice. The IL-2 serum concentrations in the mice were then measured by ELISA after 2, 4, 6, 8, 10 and 24 h. Fractionation of the transdermal IL-2 application was also examined as a means of improving uptake.
  
  
  RESULTS
  In concentrations of 25,000 and 50,000 IU IL-2, the subcutaneous application of ITFs resulted in a longer lasting IL-2 serum concentration than did the subcutaneous application of pure IL-2. While at 25,000 IU, the epicutaneous application of ITFs resulted in serum concentrations comparable to those resulting from s.c. application, at 50,000 and 150,000 IU, only 50% and 22.6% of the maximum serum concentration resulting from the s.c. application of pure IL-2 was obtained. Fractionating the transdermal IL-2 application improved uptake.
  
  
  CONCLUSIONS
  We were able to show that biologically active IL-2 can be bonded to TFs up to 75%. It is possible to transport IL-2 through the skin using TFs. Both the concentration-dependent saturation of the TFs with IL-2 and fractionation of the application resulted in differing degrees of transcutaneous IL-2 uptake.
authors.affiliation: Department of Urology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hofer
authors.forename: Heiner
authors.initials: H
authors.lastname: van Randenborgh
authors.forename: Antonie
authors.initials: A
authors.lastname: Lehmer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hartung
authors.forename: Jürgen
authors.initials: J
authors.lastname: Breul
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005374:Filtration; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D021381:Protein Transport / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D007376:Interleukin-2