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Novel sustained-release formulation strategies for vaginal administration of drug-loaded nanoparticles

School of Pharmacy | PHD
Funding
Unfunded
Reference Number
PMY/2201/07
Application Deadline
None specified
Start Date
None specified

Overview

Sustained-release drug products are useful in prolonging the action of a drug in the body by maintaining therapeutic concentrations of the drug over extended time periods. Here, we are particularly interested in developing innovative polymeric vaginal rings for long-acting vaginal administration of drug-loaded nanoparticles. Various steroid-releasing vaginal ring products are currently marketed for hormonal contraception and estrogen replacement therapy, and a new ring device – developed in part by the Queen's University Belfast (QUB) and offering sustained release of the antiretroviral drug dapivirine for HIV prevention – is due to reach market soon. However, a major limitation of current vaginal ring technologies is that they are generally not useful for administration of either large molecule drugs or drug-loaded nanoparticles, due to limited solubility and/or diffusion in the polymeric materials used to manufacture rings. Here, we propose for the first time to develop and test a novel vaginal ring developed for sustained release of drug-loaded nanoparticles, with potential applications in prevention/treatment of sexually transmitted infections, mucosal immunisation, treatment of cervicovaginal cancers, etc. The ring device comprises orifices in the ring surface which expose the underlying drug-loaded core. The ring is easy to manufacture using highly-scalable and conventional injection molding technologies.

Professor Malcolm's research group at QUB has world-leading expertise in the development of vaginal ring devices for sustained/controlled release drug delivery applications. In recent years, there has been great interest in developing vaginal rings for sustained administration of molecules beyond the hydrophobic small molecules of current marketed ring products. With ongoing advances in the development of biopharmaceuticals, new ring technologies with potential for sustained release of peptides, proteins, DNA and drug-loaded nanoparticles are of particular interest. Recently, as part of a Wellcome Trust funded project ('Chemokine-based microbicides: a pathway from a first-in-human study towards Phase 2/3 and licensure’), QUB has developed a new vaginal ring technology providing controlled release of 5P12-RANTES, a chemokine analogue that potently blocks the HIV CCR5 coreceptor. That ring is currently being evaluated in large-animal studies. Here, for the first time, we propose to evaluate this new ring technology platform for sustained release of drug-loaded nanoparticles. Previously published articles reporting vaginal administration of drug-loaded nanoparticles have relied on formulating the nanoparticles in simple vaginal gels or films, which cannot provide long- acting continuous administration. If successful, this project would open the way for enhanced vaginal administration of drug-loaded nanoparticles using vaginal ring technology.

Project Summary
Supervisor
Professor Karl Malcolm
Mode of Study

Full-time: 3 Years


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