Design of tenofovir-UC781 combination microbicide vaginal gels

Journal of Pharmaceutical Sciences
Patrick F KiserDavid R Friend

Abstract

Tenofovir (TFV) is a proven microbicide when administered topically as a vaginal gel. To improve its efficacy, TFV was combined with the nonnucleoside reverse-transcriptase inhibitor UC781 in a vaginal gel. Mixture design of experiments theory was used to define a range of gel compositions with varying rheological properties and to assess in vitro drug release and tissue retention. Experiments and computations led to the specification of three different gels referred to as a spreading gel (SG), an intermediate spreading gel (ISG), and a bolus gel (BG). These three gels, all containing 1.0% TFV and 0.1% micronized UC781, were evaluated for in vitro release, in vitro tissue retention and safety, and in vivo pharmacokinetics in the rabbit. There were some differences in in vitro release rates of UC781 (the higher the gel viscosity, the slower the release rate) across gels, while release of TFV was independent of gel type. In an organotypic human vaginal-ectocervical (VEC) tissue model, the amounts of tissue-associated TFV and UC781 were several orders of magnitude higher than their in vitro half-maximal inhibitory concentration. There were no differences in VEC tissue concentrations of TFV or UC781 between the SG, ISG, and BG. All...Continue Reading

References

Jul 26, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Nora J FrançoisDelia L Bernik
Nov 29, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Seyoum AyehunieMitchell Klausner
Feb 16, 2006·Human Reproduction·Kurt T BarnhartAlka Shaunik
Apr 20, 2006·International Journal of Pharmaceutics·J das Neves, M F Bahia
Jul 4, 2006·Journal of Biomechanical Engineering·Sarah L Kieweg, David F Katz
Jan 24, 2007·Contraception·Jill L SchwartzMarianne M Callahan
Apr 19, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Vincent C MarconiUNKNOWN South Africa Resistance Cohort Study Team
Jun 12, 2008·AIDS Research and Human Retroviruses·N NdembiUNKNOWN Uganda HIV Drug Resistance Working Group
Mar 5, 2009·Antimicrobial Agents and Chemotherapy·Carolina HerreraRobin J Shattock
May 8, 2009·Current Drug Delivery·José das NevesMaria Fernanda Bahia
Jun 1, 2010·International Journal of Pharmaceutics·Festo DamianPatrick F Kiser
Aug 6, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Fred LyagobaUNKNOWN DART Virology and Trial Team
Sep 16, 2010·Pharmaceutical Research·Alamelu MahalingamPatrick F Kiser
Oct 13, 2010·Toxicology·Seyoum AyehunieMitchell Klausner
Dec 9, 2010·Antiviral Research·Florian Hladik, Gustavo F Doncel
Feb 24, 2011·Antimicrobial Agents and Chemotherapy·Vanessa PirroneFred C Krebs
Mar 26, 2011·Expert Opinion on Pharmacotherapy·Pere Domingo, Francesc Vidal
Mar 29, 2011·Antiviral Research·Vanessa PirroneFred C Krebs
May 1, 2012·Drug Delivery and Translational Research·David F KatzMeng Kang
Apr 1, 2011·Drug Delivery and Translational Research·Meredith R ClarkDavid R Friend

❮ Previous
Next ❯

Citations

May 28, 2014·The Journal of Antimicrobial Chemotherapy·Diarmaid J MurphyR Karl Malcolm
Mar 4, 2014·Journal of Pharmaceutical Sciences·Claire J ForbesR Karl Malcolm
Feb 2, 2016·Advanced Drug Delivery Reviews·R Karl MalcolmDiarmaid J Murphy
May 3, 2015·Advanced Drug Delivery Reviews·David F KatzYajing Gao
Apr 16, 2015·Drug Delivery and Translational Research·Y GaoD F Katz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

AIDS Research and Human Retroviruses
Meredith R Clark, David R Friend
Toxicology in Vitro : an International Journal Published in Association with BIBRA
Seyoum AyehunieMitchell Klausner
Journal of Controlled Release : Official Journal of the Controlled Release Society
Claire J ForbesR Karl Malcolm
Best Practice & Research. Clinical Obstetrics & Gynaecology
Jessica L Adams, Angela D M Kashuba
© 2022 Meta ULC. All rights reserved