Infections caused by the herpes virus are among the oldest known to man. Recurrent herpes simplex labialis has been reported to affect almost one-half of the population of the United States, and 25 per cent of those affected have frequent and/or severe recurrences. Genital herpes, though not officially recognized as a disease until 1966, is currently an epidemic venereal disease. About five million Americans suffer from this problem, with an estimated one-half million individuals having become infected in 1981 alone. Although many forms of therapy have been tested, none has proven profoundly beneficial in decreasing the severity and frequency of the clinical manifestations. Systemic regimens adequate to suppress skin symptomology often result in adverse systemic effects and still may not overcome the inaccessibility to the drug of the target tissue. """"""""Drug delivery"""""""" remains the singularly most limiting factor to the effective treatment of herpes. Preliminary studies showing that interferon can be delivered across intact skin when incorporated in liposomes suggest a means of treating certain skin infections. The goal of these studies is to assess the possibility of treating virus-infected epithelial cells with liposomally entrapped interferon delivered by the transdermal route. Specifically, we wish to isolate and elucidate the factors associated with the liposomal entrapment of biologically active interferon and with its subsequent delivery through intact skin to tissue infected by virus. Since interferon's biological activity is long-lasting when in liposomes, liposomes also appear to offer a practical as well as an effective means of delivery of interferon to lesion sites. Furthermore, a systematic analysis of the parameters involved may provide a rational hypothesis and guidance for future research on the delivery of liposomal interferon by other routes of administration for the treatment of other disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022303-03
Application #
3133287
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1986-09-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Pharmacy
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Niemiec, S M; Ramachandran, C; Weiner, N (1995) Influence of nonionic liposomal composition on topical delivery of peptide drugs into pilosebaceous units: an in vivo study using the hamster ear model. Pharm Res 12:1184-8
Fleisher, D; Niemiec, S M; Oh, C K et al. (1995) Topical delivery of growth hormone releasing peptide using liposomal systems: an in vitro study using hairless mouse skin. Life Sci 57:1293-7
Egbaria, K; Ramachandran, C; Weiner, N (1990) Topical delivery of ciclosporin: evaluation of various formulations using in vitro diffusion studies in hairless mouse skin. Skin Pharmacol 3:21-8
Egbaria, K; Ramachandran, C; Kittayanond, D et al. (1990) Topical delivery of liposomally encapsulated interferon evaluated by in vitro diffusion studies. Antimicrob Agents Chemother 34:107-10
Weiner, N; Williams, N; Birch, G et al. (1989) Topical delivery of liposomally encapsulated interferon evaluated in a cutaneous herpes guinea pig model. Antimicrob Agents Chemother 33:1217-21
McLaughlin-Taylor, E; Willey, D E; Cantin, E M et al. (1988) A recombinant vaccinia virus expressing herpes simplex virus type 1 glycoprotein B induces cytotoxic T lymphocytes in mice. J Gen Virol 69 ( Pt 7):1731-4
Addicks, W J; Flynn, G L; Weiner, N et al. (1988) Drug transport from thin applications of topical dosage forms: development of methodology. Pharm Res 5:377-82
Addicks, W J; Flynn, G L; Weiner, N (1987) Validation of a flow-through diffusion cell for use in transdermal research. Pharm Res 4:337-41