An evaluation of polycaprolactone matrices for vaginal delivery of the antiviral, tenofovir, in preventing heterosexual transmission of HIV

Dang, Nhung T. T., Sivakumaran, Haran, Harrich, David and Coombes, Allan G. A. (2013) An evaluation of polycaprolactone matrices for vaginal delivery of the antiviral, tenofovir, in preventing heterosexual transmission of HIV. Journal of Pharmaceutical Sciences, 102 10: 3725-3735. doi:10.1002/jps.23684


Author Dang, Nhung T. T.
Sivakumaran, Haran
Harrich, David
Coombes, Allan G. A.
Title An evaluation of polycaprolactone matrices for vaginal delivery of the antiviral, tenofovir, in preventing heterosexual transmission of HIV
Journal name Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0022-3549
1520-6017
Publication date 2013-10
Sub-type Article (original research)
DOI 10.1002/jps.23684
Volume 102
Issue 10
Start page 3725
End page 3735
Total pages 11
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2014
Language eng
Formatted abstract
Tenofovir was incorporated in controlled-release polycaprolactone (PCL) matrices designed for production of vaginal inserts for prevention of HIV transmission. Rapid cooling of suspensions of the drug powder in PCL solution resulted in micro-porous matrices with tenofovir loadings up to 12% (w/w) and high incorporation efficiencies in excess of 90%. The release behaviour of tenofovir in simulated vaginal fluid (SVF) demonstrated high delivery efficiency of 85%–99% over 30 days and could be described effectively by a first-order kinetics model giving a mean value of 0.126 day-1 for the release constant (k1). Tenofovir released from PCL matrices into SVF exhibited high relative activity ranging from 70 to 90%, against pseudo-typed HIV-1-infected HeLa cells. The inhibitory activity of tenofovir standard solutions in SVF provided an IC50 value of 2.38 μM. Besides confirming high levels of in vitro antiviral activity, the predicted concentrations of tenofovir, which would be released from a PCL intra-vaginal ring in vivo, exceeded the IC50 value for HIV-1 by a factor of 35–200 and clinically protective concentrations by a factor of 50. These findings recommend further investigations of antiviral-loaded PCL matrices for controlling heterosexual transmission of HIV.
Keyword Intra-vaginal inserts
Microbicides
Tenofovir
HIV
Polycaprolactone matrices
Drug release
Drug delivery system
HIV/AIDS
Mathematical model
In vitro model
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Pharmacy Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 09 Sep 2013, 22:52:39 EST by Nhung Dang on behalf of School of Pharmacy