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DESIGN, DEVELOPMENT AND EVALUATION OF AN EXTENDED RELEASE VAGINAL FILM PLATFORM FOR HIV PREVENTION

Grab, Sheila (2018) DESIGN, DEVELOPMENT AND EVALUATION OF AN EXTENDED RELEASE VAGINAL FILM PLATFORM FOR HIV PREVENTION. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The human immunodeficiency virus (HIV) is a global health pandemic and over 70% of those living with HIV are found in Sub-Saharan Africa. In this region, the main method of transmission is through heterosexual contact and women account for the majority of those living with the virus. Topical pre-exposure prophylaxis is the vaginal or rectal application of a microbicide product prior to sexual intercourse to protect against HIV infection. Microbicides can be formulated into dosage forms such as; tablets, gels, films and rings. Acceptability studies have identified the film, a traditionally fast release, coitally dependent formulation as an acceptable dosage form to women. Although this dosage form is found to be safe, effective and preferred among women, there are barriers to daily and coitally dependent product usage for some women. In efforts to overcome barriers of both dosage form and dosing regimen acceptability, we propose that the vaginal film can provide a platform for extended drug delivery. We hypothesized that vaginal residence time of polymeric films could be manipulated through physical film properties and polymeric makeup of the film, which can be used to extend the dosing interval of films for the delivery of potent antiretrovirals. Increased volume films were manufactured through altering film thickness. These films were able to accommodate a hydrophilic agent, tenofovir (TFV), a hydrophobic agent, dapivirine (DPV) and a combination of dapivirine and MK-2048. Model films containing TFV and DPV were assessed in the non-human primate and showed that increased volume films can extend vaginal retention time compared to their thin film counterparts. Another approach to formulate extended release films was through a design of experiments using a combination of polymers to enhance vaginal retention. A panel of films was manufactured and characterized. A lead film platform was selected and when tested in the non-human primate was able to deliver MK-2048 vaginally at levels above the IC50 for this compound for up to 30 days. Overall, this work provided strong evidence for the application of the polymeric film as an extended release platform for the vaginal delivery of antiviral agents for HIV prevention.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Grab, Sheilasmgrab@pitt.edusmgrab
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorRohan, Lisa Clrohan@mwri.magee.edurohanl
Committee MemberBeumer, Jan Hbeumerjh@upmc.eduJHB11
Committee MemberMa, XiaochaoMXIAOCHA@pitt.eduMXIAOCHA
Committee MemberSant, VinayakVIS45@pitt.eduVIS45
Committee MemberAnderson, Carlandersonca@duq.edu
Date: 10 April 2018
Date Type: Publication
Defense Date: 27 October 2017
Approval Date: 10 April 2018
Submission Date: 10 April 2018
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 194
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: HIV prevention, vaginal film, microbicide
Date Deposited: 10 Apr 2018 14:13
Last Modified: 10 Apr 2018 14:13
URI: http://d-scholarship.pitt.edu/id/eprint/33702

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