Formulation of interleukin-2 and interferon-alpha containing ultradeformable carriers for potential transdermal application.
BACKGROUND
Transfersomes (TF) are new highly deformable hydrophilic lipid vesicles, which are able to spontaneously penetrate the skin barrier because of their characteristics. Transfersomes are able to transport non-invasively low as well as high molecular weight molecules into the body. We describe the formulation and several biological characteristics of Interleukin-2 and Interferon-a containing TF.


METHODS
TF contain natural phosphatidylcholine and sodium cholate. Recombinant human IL-2 and human hybrid interferon-alpha A/D were added to TF and incubated for 24 hours at 4 degrees C. Immunotransfersomes were isolated from free IL-2 and IFN by filtration (Centrisart, Sartorius). Biological activity of immunotransfersomes was measured by CTLL-cell-assay for IL-2 and by A549--EMCV-assay for IFN, concentrations of proteins by ELISA.


RESULTS
It has been possible to incorporate a high amount of IL-2 and IFN in TF (75-80%). Incorporated IL-2 and IFN were biological active. The increase of the proportion of lipid to protein to 90.9/1 led to growing probability of association.


CONCLUSIONS
We were able to show, that IL-2 as well as IFN is trapped by transfersomes in biological active form and in sufficient concentrations for immunotherapy. In upcoming experiments these IL-2 and IFN-containing TF are used for a transdermal approach in the murine RENCA cell line model.
Hofer
C
C
Urologische Klinik und Poliklinik, Technischen Universität München, Germany.
Göbel
R
R
Deering
P
P
Lehmer
A
A
Breul
J
J
D000279:Administration, Cutaneous; D001681:Biological Assay; D019826:Cholic Acid; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D008081:Liposomes; D010713:Phosphatidylcholines; D011994:Recombinant Proteins / Q000008:administration & dosage
D004337:Drug Carriers; D007370:Interferon Type I; D016898:Interferon-alpha; D007376:Interleukin-2; D008081:Liposomes; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D019826:Cholic Acid