This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Catalone, B. J. Articles by Wigdahl, B. Search for Related Content PubMed PubMed Citation Articles by Catalone, B. J. Articles by Wigdahl, B.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2005, p. 1509-1520, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1509-1520.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative Safety Evaluation of the Candidate Vaginal Microbicide C31G

Bradley J. Catalone,^1, Tina M. Kish-Catalone,^1, Elizabeth B. Neely,¹ Lynn R. Budgeon,² Mary L. Ferguson,¹ Catherine Stiller,¹ Shendra R. Miller,¹ Daniel Malamud,³ Fred C. Krebs,⁴ Mary K. Howett,⁵ and Brian Wigdahl^4*

Departments of Microbiology and Immunology,¹ Pathology, The Pennsylvania State University College of Medicine, Hershey,² Department of Biochemistry, University of Pennsylvania School of Dental Medicine,³ Department of Microbiology and Immunology and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine,⁴ Department of Bioscience and Biotechnology, Drexel University, Philadelphia, Pennsylvania⁵

Received 16 April 2004/ Returned for modification 28 May 2004/ Accepted 1 December 2004

C31G is currently the focus of clinical trials designed to evaluate this agent as a microbicidal and spermicidal agent. In the following studies, the in vivo safety of C31G was assessed with a Swiss Webster mouse model of cervicovaginal toxicity and correlated with results from in vitro cytotoxicity experiments and published clinical observations. A single exposure of unformulated 1% C31G resulted in mild-to-moderate epithelial disruption and inflammation at 2 and 4 h postapplication. The columnar epithelium of the cervix was the primary site of damage, while no perturbation of the vaginal mucosa was observed. In contrast, application of unformulated 1.7% C31G resulted in greater levels of inflammation in the cervical epithelium at 2 h postapplication and severe epithelial disruption that persisted to 8 h postapplication. Application of a nonionic aqueous gel formulation containing 1% C31G resulted in no apparent cervicovaginal toxicity at any time point evaluated. However, formulation of 1.7% C31G did not substantially reduce the toxicity associated with unformulated C31G at that concentration. These observations correlate with findings gathered during a recent clinical trial, in which once-daily applications resulted in no adverse events in women receiving the formulation containing 1% C31G, compared to moderate-to-severe adverse events in 30% of women receiving the 1.7% C31G formulation. The Swiss Webster mouse model was able to effectively discriminate between concentrations and formulations of C31G that produced distinct clinical effects in human trials. The Swiss Webster animal model may be a highly valuable tool for preclinical evaluation of candidate vaginal microbicides.

---

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Ln., Philadelphia, PA 19129. Phone: (215) 991-8352. Fax: (215) 848-2271. E-mail: brian.wigdahl{at}drexel.edu.

Present address: Chesapeake Biological Laboratories, Inc., Baltimore, MD 21230.

Present address: Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, MD 21201.

---

Antimicrobial Agents and Chemotherapy, April 2005, p. 1509-1520, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1509-1520.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Jain, R. K., Jain, A., Maikhuri, J. P., Sharma, V. L., Dwivedi, A. K., Kiran Kumar, S.T.V.S., Mitra, K., Bajpai, V. K., Gupta, G. (2009). In vitro testing of rationally designed spermicides for selectively targeting human sperm in vagina to ensure safe contraception. Hum Reprod 24: 590-601 [Abstract] [Full Text]  
• Jain, R.K., Maikhuri, J.P., Kiran Kumar, S.T.V.S., Sharma, V.L., Dwivedi, A.K., Mitra, K., Bajpai, V.K., Gupta, G. (2007). Novel disulphide esters of carbothioic acid as potent, non-detergent spermicides with low toxicity to Lactobacillus and HeLa cells in vitro. Hum Reprod 22: 708-716 [Abstract] [Full Text]