We have developed formulations of a C31 G-based microbicide which maintains potent anti-bacterial and anti-viral activity when tested with in vitro and animal test systems. In this proposal we will expand our repertoire of surfactant-based formulations and analyze the physical characteristics and release of active drug from these formulations. Subsequently vaginal model systems, based on data obtained from in vivo human studies, will be used to evaluate microbicidal efficacy. (1) What are the characteristics and kinetics of release of active microbicide from C31G and C31G/alkyl sulfate formulations as compared to commercial (N-9) formulations? (2) When a microbicide is introduced into the vagina what are the dynamics of mixing with resident fluids? (3) What is the distribution and substantivity of formulations within the vagina, and what factors influence these events? (4) The results of these experiments will allow us to ask the most important biological question, namely how effective are the microbicide formulations at killing bacterial and vaginal pathogens under conditions that closely mimic the in vivo situation? To address these questions we propose to develop a series of models of increasing complexity, beginning with classical pharmaceutical release method, followed by determining the effects of added cervical, vaginal and seminal fluids. This will permit an evaluation of microbicidal activity under conditions that mimic the local vaginal environment. Key experiments will be replicated in human volunteers and in the human vaginal xenograft model, to determine how close the in vivo measurements reflect the in vivo situation.

Project Start
2000-09-01
Project End
2001-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
6
Fiscal Year
2000
Total Cost
$58,217
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Passic, Shendra R; Ferguson, Mary Lee; Catalone, Bradley J et al. (2010) Structure-activity relationships of polybiguanides with activity against human immunodeficiency virus type 1. Biomed Pharmacother 64:723-32
Pavlovic, Jelena; Floros, Joanna; Phelps, David S et al. (2008) Differentiation of xenografted human fetal lung parenchyma. Early Hum Dev 84:181-93
Beer, Brigitte E; Doncel, Gustavo F; Krebs, Fred C et al. (2006) In vitro preclinical testing of nonoxynol-9 as potential anti-human immunodeficiency virus microbicide: a retrospective analysis of results from five laboratories. Antimicrob Agents Chemother 50:713-23
Fang, L; Meyers, C; Budgeon, L R et al. (2006) Induction of productive human papillomavirus type 11 life cycle in epithelial cells grown in organotypic raft cultures. Virology 347:28-35
Hartmann, Sandra Urdaneta; Wigdahl, Brian; Neely, Elizabeth B et al. (2006) Biochemical analysis of human milk treated with sodium dodecyl sulfate, an alkyl sulfate microbicide that inactivates human immunodeficiency virus type 1. J Hum Lact 22:61-74
Deka, Srilekha; Vanover, Jennifer; Dessus-Babus, Sophie et al. (2006) Chlamydia trachomatis enters a viable but non-cultivable (persistent) state within herpes simplex virus type 2 (HSV-2) co-infected host cells. Cell Microbiol 8:149-62
Hartmann, Sandra Urdaneta; Berlin, Cheston M; Howett, Mary K (2006) Alternative modified infant-feeding practices to prevent postnatal transmission of human immunodeficiency virus type 1 through breast milk: past, present, and future. J Hum Lact 22:75-88; quiz 89-93
Fang, L; Budgeon, L R; Doorbar, J et al. (2006) The human papillomavirus type 11 E1/E4 protein is not essential for viral genome amplification. Virology 351:271-9
Urdaneta, Sandra; Wigdahl, Brian; Neely, Elizabeth B et al. (2005) Inactivation of HIV-1 in breast milk by treatment with the alkyl sulfate microbicide sodium dodecyl sulfate (SDS). Retrovirology 2:28
Krebs, Fred C; Miller, Shendra R; Ferguson, Mary Lee et al. (2005) Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1. Biomed Pharmacother 59:438-45

Showing the most recent 10 out of 35 publications