In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients

Antiviral Research

Volumn 96, Issue 2, 2012, Pages 226-233

  Grammen, Carolien ^a   Augustijns, Patrick ^a   Brouwers, Joachim ^a  

^a DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

Author keywords

HIV microbicide; Permeability; Solubility; Vaginal gel

Indexed keywords

CYCLODEXTRIN; DAPIVIRINE; DARUNAVIR; ELASTOMER; EXCIPIENT; MACROGOL 10000; SAQUINAVIR; SILICONE; TENOFOVIR;

AQUEOUS SOLUTION; ARTICLE; DRUG EFFICACY; DRUG FORMULATION; DRUG PENETRATION; DRUG SOLUBILITY; GEL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VITRO STUDY; PRIORITY JOURNAL; VAGINA MUCOSA; VIRUS TRANSMISSION;

ANTI-HIV AGENTS; ANTI-INFECTIVE AGENTS; EXCIPIENTS; FEMALE; HUMANS; MODELS, THEORETICAL; MUCOUS MEMBRANE; PERMEABILITY; SOLUBILITY; VAGINA;

EID: 84867236136     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2012.09.011     Document Type: Article

References (27)

1. Abdool Karim Q., Abdool Karim S.S., Frohlich J.A., Grobler A.C., Baxter C., Mansoor L.E., Kharsany A.B.M., Sibeko S., Mlisana K.P., Omar Z., Gengiah T.N., Maarschalk S., Arulappan N., Mlotshwa M., Morris L., Taylor D. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010, 329:1168-1174.
2. Adams J.L., Kashuba A.D.M. Formulation, pharmacokinetics and pharmacodynamics of topical microbicides. Best Pract. Res. Clin. Obstet. Gynaecol. 2012, 26:451-462.
3. Ayehunie S., Cannon C., Lamore S., Kubilus J., Anderson D.J., Pudney J., Klausner M. Organotypic human vaginal-ectocervical tissue model for irritation studies of spermicides, microbicides, and feminine-care products. Toxicol. In Vitro 2006, 20:689-698.
4. Brouwers J., Vermeire K., Grammen C., Schols D., Augustijns P. Early identification of availability issues for poorly water-soluble microbicide candidates in biorelevant media: a case study with saquinavir. Antiviral Res. 2011, 91:217-223.
5. Cal K., Centkowska K. Use of cyclodextrins in topical formulations: practical aspects. Eur. J. Pharm. Biopharm. 2008, 68:467-478.
6. Clark, M.R., Friend, D.R., in press. Pharmacokinetics and topical vaginal effects of two tenofovir gels in rabbits. AIDS Res. Hum. Retrov.
7. ClinicalTrials.gov. at <> (accessed on 2.07.12). http://clinicaltrials.gov/.
8. D'Cruz O.J., Uckun F.M. Preclinical evaluation of a dual-acting microbicidal prodrug WHI-07 in combination with vanadocene dithiocarbamate in the female reproductive tract of rabbit, pig, and cat. Toxicol. Pathol. 2007, 35:910-927.
9. Dezzutti C.S., Rohan L.C., Wang L., Uranker K., Shetler C., Cost M., Lynam J.D., Friend D. Reformulated tenofovir gel for use as a dual compartment microbicide. J. Antimicrob. Chemother. 2012, 67:2139-2142.
10. Dobard C., Sharma S., Martin A., Pau C.-P., Holder A., Kuklenyik Z., Lipscomb J., Hanson D.L., Smith J., Novembre F.J., García-Lerma J.G., Heneine W. Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue. J. Virol. 2012, 86:718-725.
11. Fletcher P., Harman S., Azijn H., Armanasco N., Manlow P., Perumal D., de Bethune M.-P., Nuttall J., Romano J., Shattock R. Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor. Antimicrob. Agents Chemother. 2009, 53:487-495.
12. Forbes C.J., Lowry D., Geer L., Veazey R.S., Shattock R.J., Klasse P.J., Mitchnick M., Goldman L., Doyle L.A., Muldoon B.C.O., Woolfson A.D., Moore J.P., Malcolm R.K. Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc. J. Control. Release 2011, 156:161-169.
13. Gali Y., Ariën K.K., Praet M., Van den Bergh R., Temmerman M., Delezay O., Vanham G. Development of an in vitro dual-chamber model of the female genital tract as a screening tool for epithelial toxicity. J. Virol. Methods 2010, 165:186-197.
14. Gali Y., Delezay O., Brouwers J., Addad N., Augustijns P., Bourlet T., Hamzeh-Cognasse H., Ariën K.K., Pozzetto B., Vanham G. In vitro evaluation of viability, integrity, and inflammation in genital epithelia upon exposure to pharmaceutical excipients and candidate microbicides. Antimicrob. Agents Chemother. 2010, 54:5105-5114.
15. Hillier S.L., Moench T., Shattock R., Black R., Reichelderfer P., Veronese F. In vitro and in vivo: the story of nonoxynol 9. J. Acquir. Immune Defic. Syndr. 2005, 39:1-8.
16. Hladik F., Doncel G.F. Preventing mucosal HIV transmission with topical microbicides: challenges and opportunities. Antiviral Res. 2010, 88(Suppl. 1):S3-9.
17. Kiser P.F., Mahalingam A., Fabian J., Smith E., Damian F.R., Peters J.J., Katz D.F., Elgendy H., Clark M.R., Friend D.R. Design of tenofovir-UC781 combination microbicide vaginal gels. J. Pharm. Sci. 2012, 101:1852-1864.
18. Loftsson T., Brewster M.E. Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes. J. Pharm. Pharmacol. 2011, 63:1119-1135.
19. Miller C.J., Li Q., Abel K., Kim E.-Y., Ma Z.-M., Wietgrefe S., La Franco-Scheuch L., Compton L., Duan L., Shore M.D., Zupancic M., Busch M., Carlis J., Wolinsky S., Wolinksy S., Haase A.T. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J. Virol. 2005, 79:9217-9227.
20. Nel A.M., Coplan P., van de Wijgert J.H., Kapiga S.H., von Mollendorf C., Geubbels E., Vyankandondera J., Rees H.V., Masenga G., Kiwelu I., Moyes J., Smythe S.C. Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women. AIDS 2009, 23:1531-1538.
21. Nel A., Smythe S., Young K., Malcolm K., McCoy C., Rosenberg Z., Romano J. Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women. J. Acquir. Immune Defic. Syndr. 2009, 51:416-423.
22. Owen D.H., Katz D.F. A vaginal fluid simulant. Contraception 1999, 59:91-95.
23. Rohan L.C., Moncla B.J., Kunjara Na Ayudhya R.P., Cost M., Huang Y., Gai F., Billitto N., Lynam J.D., Pryke K., Graebing P., Hopkins N., Rooney J.F., Friend D., Dezzutti C.S. In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide. PLoS ONE 2010, 5:e9310.
24. Stolte-Leeb N., Loddo R., Antimisiaris S., Schultheiss T., Sauermann U., Franz M., Mourtas S., Parsy C., Storer R., La Colla P., Stahl-Hennig C. Topical nonnucleoside reverse transcriptase inhibitor MC 1220 partially prevents vaginal RT-SHIV infection of macaques. AIDS Res. Hum. Retroviruses 2011, 27:933-943.
25. van de Waterbeemd H., Lennernäs H., Artursson P. Drug Bioavailability. Estimation of Solubility, Permeability, Absorption and Bioavailability 2003, Wiley-VCH, Weinheim.
26. WHO | Gender inequalities and HIV. WHO at <> (accessed on 2.07.12). http://www.who.int/gender/hiv_aids/en/.
27. Woolfson A.D., Umrethia M.L., Kett V.L., Malcolm R.K. Freeze-dried, mucoadhesive system for vaginal delivery of the HIV microbicide, dapivirine: optimisation by an artificial neural network. Int. J. Pharm. 2010, 388:136-143.