Vaginal Microbicide Film Combinations of Two Reverse Transcriptase Inhibitors, EFdA and CSIC, for the Prevention of HIV-1 Sexual Transmission

Pharmaceutical Research
Wei ZhangLisa C Rohan

Abstract

EFdA is a potent nucleoside reverse transcriptase inhibitor (NRTI) with activity against a wide spectrum of wild-type and drug resistant HIV-1 variants. CSIC is a tight-binding non-nucleoside reverse transcriptase inhibitor (NNRTI) with demonstrated anti-HIV properties important for use in topical prevention of HIV transmission. The objective of this study was to develop and characterize film-formulated EFdA and CSIC for use as a female-controlled vaginal microbicide to prevent sexual transmission of HIV. Assessments of EFdA- and CSIC-loaded films included physicochemical characteristics, in vitro cytotoxicity, epithelia integrity studies, compatibility with the normal vaginal Lactobacillus flora and anti-HIV bioactivity evaluations. No significant change in physicochemical properties or biological activity of the combination films were noted during 3 months storage. In vitro cytotoxicity and bioactivity testing showed that 50% cytotoxic concentration (CC50) of either EFdA or CSIC was several orders of magnitude higher than the 50% effective concentration (EC50) values. Film-formulated EFdA and CSIC combination showed additive inhibitory activity against wild type and drug-resistant variants of HIV. Epithelial integrity studies...Continue Reading

References

Oct 9, 2001·HIV Clinical Trials·UNKNOWN Panel on Clinical Practices for Treatment of HIV Infection
May 26, 2005·Contraception·Elizabeth G RaymondRichard Blackwell
Jul 26, 2005·Sexually Transmitted Diseases·Bernard J Moncla, Sharon L Hillier
Jul 6, 2006·JAMA : the Journal of the American Medical Association·Bridget M Kuehn
May 20, 2008·The International Journal of Biochemistry & Cell Biology·Atsushi KawamotoMasao Matsuoka
Feb 6, 2009·The AAPS Journal·Lisa Cencia Rohan, Alexandra B Sassi
Dec 5, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Todd J JohnsonPatrick F Kiser
Jan 20, 2011·Antimicrobial Agents and Chemotherapy·Alamelu MahalingamPatrick F Kiser
Jan 10, 2012·Journal of Microbiological Methods·B J MonclaH Yang
Jan 24, 2012·Current HIV Research·Robert W Buckheit, Karen W Buckheit
Mar 7, 2012·Pharmaceutical Research·Anthony S HamRobert W Buckheit
Jun 26, 2013·Antimicrobial Agents and Chemotherapy·Atsuko HachiyaStefan G Sarafianos
Jul 12, 2013·Drug Development and Industrial Pharmacy·Wei ZhangLisa C Rohan
Jun 28, 2014·The Journal of Biological Chemistry·Eleftherios MichailidisStefan G Sarafianos

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Citations

Aug 19, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Minlu HuLisa C Rohan
Nov 5, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Cassilda Cunha-ReisJosé das Neves
Apr 27, 2018·Current Opinion in HIV and AIDS·Martin Markowitz, Stefan G Sarafianos
Aug 22, 2017·Therapeutic Delivery·Anthony S Ham, Robert W Buckheit
Apr 10, 2020·Expert Opinion on Drug Metabolism & Toxicology·Megan NearyAdeniyi Olagunju
Apr 24, 2019·Pharmaceuticals·Kamal SinghAnders Sönnerborg
Oct 7, 2017·Journal of Pharmaceutical Innovation·Tiantian GongLisa C Rohan
Jun 17, 2020·Colloids and Surfaces. B, Biointerfaces·Manali PatkiKetan Patel
Jul 3, 2021·Pharmaceutics·Tomasz OsmałekBozena Michniak-Kohn
Jul 20, 2021·Advanced Drug Delivery Reviews·José das NevesBruno Sarmento
Aug 24, 2021·The Journal of Antimicrobial Chemotherapy·Kenji NishiuraCharles Dobard

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