Vaginal microbicide gel for delivery of IQP-0528, a pyrimidinedione analog with a dual mechanism of action against HIV-1

Antimicrobial Agents and Chemotherapy

Volumn 55, Issue 4, 2011, Pages 1650-1660

  Mahalingam, Alamelu ^a   Simmons, Adam P ^b   Ugaonkar, Shweta R ^b   Watson, Karen M ^c   Dezzutti, Charlene S ^d   Rohan, Lisa C ^d   Buckheit Jr , Robert W ^c   Kiser, Patrick F ^a,b  

^a UNIVERSITY OF UTAH   (United States)

^b Department of Electrical and Computer Engineering   (United States)

^c ImQuest Biosciences   (United States)

^d UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOMER; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; HYDROXYETHYLCELLULOSE; IQP 0406; IQP 0407; IQP 0408; IQP 0410; IQP 0528; IQP 0530; IQP 0532; IQP 0558; IQP 1187; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED DRUG RELEASE; CONTROLLED STUDY; CULTURE MEDIUM; DRUG ACTIVITY; DRUG DELIVERY SYSTEM; DRUG DIFFUSION; DRUG FORMULATION; DRUG PENETRATION; DRUG SAFETY; DRUG SCREENING; DRUG STABILITY; DRUG UPTAKE; EXPLANT; FEMALE; GEL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN TISSUE; NONHUMAN; PRIORITY JOURNAL; VIRUS ENTRY; VIRUS INHIBITION;

ANIMALS; ANTI-HIV AGENTS; FEMALE; HIV-1; HUMANS; PYRIMIDINONES; SWINE; VAGINA; VAGINAL CREAMS, FOAMS, AND JELLIES;

EID: 79953196872     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01368-10     Document Type: Article

References (42)

1. Abdool Karim, Q., et al. 2010. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168-1174.
2. Ayehunie, S., et al. 2006. Organotypic human vaginal-ectocervical tissue model for irritation studies of spermicides, microbicides, and feminine-care products. Toxicol. In Vitro 20:689-698. (Pubitemid 43816250)
3. Buckheit, R. W., Jr., L. H. Tracy, M. W. Karen, S.-G. Chung, and E.-H. Cho. 2008. Comparative evaluation of the inhibitory activities of a series of pyrimidinedione congeners that inhibit human immunodeficiency virus types 1 and 2. Antimicrob. Agents Chemother. 52:225-236.
4. Buckheit, R. W., Jr., et al. 2007. The structure-activity relationships of 2,4(1H,3H)-pyrimidinedione derivatives as potent HIV type 1 and type 2 inhibitors. Antivir. Chem. Chemother. 18:259-275.
5. Buckheit, R. W., Jr., et al. 2001. SJ-3366, a unique and highly potent non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2. Antimicrob. Agents Chemother. 45:393-400.
6. Cone, R. A., et al. 2006. Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission. BMC Infect. Dis. 6:90.
7. Cummins, J. E., Jr., et al. 2007. Preclinical testing of candidate topical microbicides for anti-human immunodeficiency virus type 1 activity and tissue toxicity in a human cervical explant culture. Antimicrob. Agents Chemother. 51:1770-1779.
8. Dezzutti, C. S., et al. 2004. In vitro comparison of topical microbicides for prevention of human immunodeficiency virus type 1 transmission. Antimicrob. Agents Chemother. 48:3834-3844.
9. das Neves, J., and M. F. Bahia. 2006. Gels as vaginal drug delivery systems. Int. J. Pharm. 318:1-14.
10. Gibaldi, M., M. Lee, and A. Desai. 2007. Gibaldi's drug delivery systems in pharmaceutical care. American Society of Health-System Pharmacists, Bethesda, MD.
11. Fichorova, R. N., and D. J. Anderson. 1999. Differential expression of immunobiological mediators by immortalized human cervical and vaginal epithelial cells. Biol. Reprod. 60:508-514.
12. Fichorova, R. N., et al. 2004. Interleukin (IL)-1, IL-6, and IL-8 predict mucosal toxicity of vaginal microbicidal contraceptives. Biol. Reprod. 71:761-769.
13. Flynn, G. L., et al. 1999. Assessment of value and applications of in vitro testing of topical dermatological drug products. Pharm. Res. 16:1325-1330.
14. Garg, A. B., J. Nuttall, and J. Romano. 2008. The future of HIV microbicides: challenges and opportunities. Antivir. Chem. Chemother. 19:143-150.
15. Grabovac, V., D. Guggi, and A. Bernkop-Schnürch. 2005. Comparison of the mucoadhesive properties of various polymers. Adv. Drug Deliv. Rev. 57: 1713-1723.
16. Grant, R. M., et al. 2008. Whither or wither microbicides? Science 321:532-534.
17. Gupta, K. M., et al. 2008. Polyurethane intravaginal ring for controlled delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1. J. Pharm. Sci. 97:4228-4239.
18. Hadgraft, J., and M. E. Lane. 2005. Skin permeation: the years of enlightenment. Int. J. Pharm. 305:2-12.
19. Higuchi, W. I. 1962. Analysis of data on the medicament release from ointments. J. Pharm. Sci. 51:802-804.
20. Klasse, P. J., R. Shattock, and J. P. Moore. 2008. Antiretroviral drug-based microbicides to prevent HIV-1 sexual transmission. Annu. Rev. Med. 59: 455-471.
21. Kulkarni, U., R. Mahalingam, I. Pather, X. Li, and B. Jasti. 2010. Porcine buccal mucosa as in vitro model: effect of biological and experimental variables. J. Pharm. Sci. 99:1265-1277.
22. Lewi, P., et al. 2004. Correlations between factors determining the pharmacokinetics and antiviral activity of HIV-1 non-nucleoside reverse transcriptase inhibitors of the diaryltriazine and diarylpyrimidine classes of compounds. Drugs 5:245-257. (Pubitemid 39429513)
23. Mahalingam, A., et al. 2010. Design of a semisolid vaginal microbicide gel by relating composition to properties and performance. Pharm. Res. 27:2478-2491.
24. Milligan, G. N., K. L. Dudley, N. Bourne, A. Reece, and L. R. Stanberry. 2002. Entry of inflammatory cells into the mouse vagina following application of candidate microbicides: comparison of detergent-based and sulfated polymer-based agents. Sex. Transm. Dis. 29:597-605.
25. Owen, D. H., J. J. Peters, and D. F. Katz. 2000. Rheological properties of contraceptive gels. Contraception 62:321-326.
26. Rohan, L. C., et al. 2010. In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide. PLoS One 5:e9310.
27. Schoofs, M., and P. Wonacott. 2010. New tenofovir gel cuts risk of HIV infection for women in study. 18th International AIDS Conference, Vienna, Austria.
28. Singla, A. K., M. Chawla, and A. Singh. 2000. Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review. Drug Dev. Ind. Pharm. 26:913-924.
29. Smith, S. M. 2004. Pre-exposure chemoprophylaxis for HIV: it is time. Retrovirology 1:16.
30. Squier, C. A., M. J. Mantz, P. M. Schlievert, and C. C. Davis. 2008. Porcine vagina ex vivo as a model for studying permeability and pathogenesis in mucosa. J. Pharm. Sci. 97:9-21.
31. Stein, Z. A. 1990. HIV prevention: the need for methods women can use. Am. J. Public Health 80:460-462. (Pubitemid 20105954)
32. Terrazas-Aranda, K., Y. Van Herrewege, P. J. Lewi, J. Van Roey, and G. Vanham. 2007. In vitro pre- and post-exposure prophylaxis using HIV inhibitors as microbicides against cell-free or cell-associated HIV-1 infection. Antivir. Chem. Chemother. 18:141-151.
33. Tien, D., et al. 2005. In vitro and in vivo characterization of a potential universal placebo designed for use in vaginal microbicide clinical trials. AIDS Res. Hum. Retrovir. 21:845-853.
34. Uchegbu, I. F., and A. G. Schätzlein. 2006. Polymers in drug delivery. CRC/Taylor & Francis, Boca Raton, FL.
35. Valenta, C. 2005. The use of mucoadhesive polymers in vaginal delivery. Adv. Drug Deliv. Rev. 57:1692-1712.
36. van Eyk, A. D., and P. van der Biijl. 2006. Comparative permeability of fresh and frozen/thawed porcine buccal mucosa toward various chemical markers. SADJ 61:200-203.
37. van Eyk, A. D., and P. van der Bijl. 2005. Porcine vaginal mucosa as an in vitro permeability model for human vaginal mucosa. Int. J. Pharm. 305:105-111.
38. Vermani, K., and S. Garg. 2000. The scope and potential of vaginal drug delivery. Pharm. Sci. Technol. Today 3:359-364.
39. Walters, K. A. 2002. Dermatological and transdermal formulations. M. Dekker, New York, NY.
40. Wilson, D. P., P. M. Coplan, M. A. Wainberg, and S. M. Blower. 2008. The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics. Proc. Natl. Acad. Sci. U. S. A. 105:9835-9840.
41. Woolfson, A. D., R. K. Malcolm, and R. Gallagher. 2000. Drug delivery by the intravaginal route. Crit. Rev. Ther. Drug Carrier Syst. 17:509-555.
42. Youle, M., and M. A. Wainberg. 2003. Pre-exposure chemoprophylaxis (PREP) as an HIV prevention strategy. J. Int. Assoc. Physicians AIDS Care 2:102-105.