Development and in vitro evaluation of a vaginal microbicide gel formulation for UAMC01398, a novel diaryltriazine NNRTI against HIV-1

Antiviral Research

Volumn 101, Issue 1, 2014, Pages 113-121

  Grammen, Carolien ^a   Ariën, Kevin K ^b   Venkatraj, Muthusamy ^c   Joossens, Jurgen ^c   Van Der Veken, Pieter ^c   Heeres, Jan ^c   Lewi, Paul J ^c   Haenen, Steven ^a   Augustyns, Koen ^c   Vanham, Guido ^b,c   Augustijns, Patrick ^a   Brouwers, Joachim ^a  

^a DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

^b INSTITUTE OF TROPICAL MEDICINE   (Belgium)

^c UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Anti HIV microbicide; Biopharmaceutical profiling; In vitro toxicity; Vaginal flux; Vaginal gel formulation

Indexed keywords

HYDROXYETHYLCELLULOSE; MICROBICIDE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; UAMC01398; UNCLASSIFIED DRUG; AGENTS USED INTRAVAGINALLY; ANTIINFECTIVE AGENT; EXCIPIENT; MARAVIROC; METHYL PARABEN; PROPYL PARABEN; SORBIC ACID; TRIAZINE DERIVATIVE; UAMC 01398;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG FORMULATION; DRUG PENETRATION; DRUG SAFETY; DRUG SCREENING; DRUG SOLUBILITY; DRUG STABILITY; EPITHELIUM CELL; GEL; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VITRO STUDY; PRIORITY JOURNAL; TOXICITY TESTING; ANTI-HIV MICROBICIDE; BIOPHARMACEUTICAL PROFILING; CHEMISTRY; DISEASE TRANSMISSION; DRUG EFFECT; FEMALE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VITRO TOXICITY; PERMEABILITY; SOLUBILITY; VAGINAL FLUX; VAGINAL GEL FORMULATION; COMPARATIVE STUDY; DRUG UPTAKE; FLOW KINETICS; HYDROPHOBICITY; PH; SHEAR STRESS; TOXICITY; VISCOSITY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTI-HIV MICROBICIDE; BIOPHARMACEUTICAL PROFILING; IN VITRO TOXICITY; VAGINAL FLUX; VAGINAL GEL FORMULATION;

ANTI-INFECTIVE AGENTS; DISEASE TRANSMISSION, INFECTIOUS; DRUG COMPOUNDING; DRUG STABILITY; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; PERMEABILITY; SOLUBILITY; VAGINAL CREAMS, FOAMS, AND JELLIES;

EID: 84889969692     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2013.11.005     Document Type: Article

References (26)

1. Q. Abdool Karim, S.S. Abdool Karim, J.A. Frohlich, A.C. Grobler, C. Baxter, L.E. Mansoor, A.B.M. Kharsany, S. Sibeko, K.P. Mlisana, Z. Omar, T.N. Gengiah, S. Maarschalk, N. Arulappan, M. Mlotshwa, L. Morris, D. Taylor, and CAPRISA 004 Trial Group Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women Science 329 2010 1168 1174
2. J.L. Adams, and A.D.M. Kashuba Formulation, pharmacokinetics and pharmacodynamics of topical microbicides Best Pract. Res. Clin. Obstet. Gynaecol. 26 2012 451 462
3. K.K. Ariën, M. Venkatraj, J. Michiels, J. Joossens, K. Vereecken, P. Van der Veken, S. Abdellati, V. Cuylaerts, T. Crucitti, L. Heyndrickx, J. Heeres, K. Augustyns, P.J. Lewi, and G. Vanham Diaryltriazine non-nucleoside reverse transcriptase inhibitors are potent candidates for pre-exposure prophylaxis in the prevention of sexual HIV transmission J. Antimicrob. Chemother. 68 2013 2038 2047
4. S. Ayehunie, C. Cannon, S. Lamore, J. Kubilus, D.J. Anderson, J. Pudney, and M. Klausner Organotypic human vaginal-ectocervical tissue model for irritation studies of spermicides, microbicides, and feminine-care products Toxicol. In Vitro 20 2006 689 698 (Pubitemid 43816250)
5. M.R. Clark, and D.R. Friend Pharmacokinetics and topical vaginal effects of two tenofovir gels in rabbits AIDS Res. Hum. Retroviruses 28 2012 1458 1466
6. T. Dahl, G.X. He, and G. Samuels Effect of hydrogen peroxide on the viscosity of a hydroxyethylcellulose-based gel Pharm. Res. 15 1998 1137 1140 (Pubitemid 28356935)
7. C.S. Dezzutti, L.C. Rohan, L. Wang, K. Uranker, C. Shetler, M. Cost, J.D. Lynam, and D. Friend Reformulated tenofovir gel for use as a dual compartment microbicide J. Antimicrob. Chemother. 67 2012 2139 2142
8. M. Gafos, M. Mzimela, S. Sukazi, R. Pool, C. Montgomery, and J. Elford Intravaginal insertion in KwaZulu-Natal: sexual practices and preferences in the context of microbicide gel use Cult. Health Sex. 12 2010 929 942
9. Y. Gali, K.K. Ariën, M. Praet, R. Van den Bergh, M. Temmerman, O. Delezay, and G. Vanham Development of an in vitro dual-chamber model of the female genital tract as a screening tool for epithelial toxicity J. Virol. Methods 165 2010 186 197
10. Y. Gali, O. Delezay, J. Brouwers, N. Addad, P. Augustijns, T. Bourlet, H. Hamzeh-Cognasse, K.K. Ariën, B. Pozzetto, and G. Vanham In vitro evaluation of viability, integrity, and inflammation in genital epithelia upon exposure to pharmaceutical excipients and candidate microbicides Antimicrob. Agents Chemother. 54 2010 5105 5114
11. C. Grammen, P. Augustijns, and J. Brouwers In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients Antiviral Res. 96 2012 226 233
12. P.F. Kiser, A. Mahalingam, J. Fabian, E. Smith, F.R. Damian, J.J. Peters, D.F. Katz, H. Elgendy, M.R. Clark, and D.R. Friend Design of tenofovir-UC781 combination microbicide vaginal gels J. Pharm. Sci. 101 2012 1852 1864
13. D.W. Ludovici, R.W. Kavash, M.J. Kukla, C.Y. Ho, H. Ye, B.L. De Corte, K. Andries, M.P. De Béthune, H. Azijn, R. Pauwels, H.E. Moereels, J. Heeres, L.M. Koymans, M.R. De Jonge, K.J. Van Aken, F.F. Daeyaert, P.J. Lewi, K. Das, E. Arnold, and P.A. Janssen Evolution of anti-HIV drug candidates. Part 2: diaryltriazine (DATA) analogues Bioorg. Med. Chem. Lett. 11 2001 2229 2234 (Pubitemid 32781672)
14. R.K. Malcolm, C.J. Forbes, L. Geer, R.S. Veazey, L. Goldman, P. Johan Klasse, and J.P. Moore Pharmacokinetics and efficacy of a vaginally administered maraviroc gel in rhesus macaques J. Antimicrob. Chemother. 68 2013 678 683
15. K.H. Mayer, L.A. Maslankowski, F. Gai, W.M. El-Sadr, J. Justman, A. Kwiecien, B. Mâsse, S.H. Eshleman, C. Hendrix, K. Morrow, J.F. Rooney, and L. Soto-Torres Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women AIDS 20 2006 543 551 (Pubitemid 43731598)
16. C.J. Miller, Q. Li, K. Abel, E.-Y. Kim, Z.-M. Ma, S. Wietgrefe, L. La Franco-Scheuch, L. Compton, L. Duan, M.D. Shore, M. Zupancic, M. Busch, J. Carlis, S. Wolinsky, S. Wolinksy, and A.T. Haase Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus J. Virol. 79 2005 9217 9227 (Pubitemid 40934833)
17. G.C. Morris, and C.J.N. Lacey Microbicides and HIV prevention: lessons from the past, looking to the future Curr. Opin. Infect. Dis. 23 2010 57 63
18. A.M. Nel, P. Coplan, S.C. Smythe, K. McCord, M. Mitchnick, P.E. Kaptur, and J. Romano Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women AIDS Res. Hum. Retroviruses 26 2010 1181 1190
19. Lactate Dehydrogenase (LDH) Assay Protocol, 2013. Ops Diagnostic at http://opsdiagnostics.com/applications/, accessed on 6/08/2013.
20. D.H. Owen, and D.F. Katz A vaginal fluid simulant Contraception 59 1999 91 95 (Pubitemid 29244754)
21. V. Pillay, F. Mashingaidze, Y.E. Choonara, L.C. Du Toit, E. Buchmann, V. Maharaj, V.M.K. Ndesendo, and P. Kumar Qualitative and quantitative intravaginal targeting: key to anti-HIV-1 microbicide delivery from test tube to in vivo success J. Pharm. Sci. 101 2012 1950 1968
22. L.C. Rohan, B.J. Moncla, R.P. Kunjara Na Ayudhya, M. Cost, Y. Huang, F. Gai, N. Billitto, J.D. Lynam, K. Pryke, P. Graebing, N. Hopkins, J.F. Rooney, D. Friend, and C.S. Dezzutti In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide PLoS ONE 5 2010 e9310
23. D. Tien, R.L. Schnaare, F. Kang, G. Cohl, T.J. McCormick, T.R. Moench, G. Doncel, K. Watson, R.W. Buckheit, M.G. Lewis, J. Schwartz, K. Douville, and J.W. Romano In vitro and in vivo characterization of a potential universal placebo designed for use in vaginal microbicide clinical trials AIDS Res. Hum. Retroviruses 21 2005 845 853 (Pubitemid 43150316)
24. A. Vallely, L. Fitzgerald, V. Fiya, H. Aeno, A. Kelly, J. Sauk, M. Kupul, J. Neo, J. Millan, P. Siba, and J.M. Kaldor Intravaginal practices and microbicide acceptability in Papua New Guinea: implications for HIV prevention in a moderate-prevalence setting BMC Res. Notes 5 2012 613
25. WHO, 2013. Microbicides at http://www.who.int/hiv/topics/microbicides/ microbicides/en/, accessed on 6/08/2013.
26. Y. Zhang, Y. Liu, W. Liu, Y. Gan, and C. Zhou Characterization of the inclusion complex of β-cyclodextrin with sorbic acid in the solid state and in aqueous solution J. Incl. Phenom. Macrocycl. Chem. 67 2010 177 182