Design, formulation and evaluation of novel dissolving microarray patches containing a long-acting rilpivirine nanosuspension

Maelíosa T.C Mc Crudden,Eneko Larrañeta,Annie Clark,Courtney Jarrahian,Annie Rein-Weston,Sophie Lachau-Durand,Nico Niemeijer,Peter Williams,Clement Haeck,Helen O Mccarthy,Darin Zehrung,Ryan F Donnelly

doi:10.1016/j.jconrel.2018.11.002

Maelíosa T.C Mc Crudden, Eneko Larrañeta + Show 10 more

Open Access

https://doi.org/10.1016/j.jconrel.2018.11.002

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Abstract

One means of combating the spread of human immunodeficiency virus (HIV) is through the delivery of long-acting, antiretroviral (ARV) drugs for prevention and treatment. The development of a discreet, self-administered and self-disabling delivery vehicle to deliver such ARV drugs could obviate compliance issues with daily oral regimens. Alternatives in development, such as long-acting intramuscular (IM) injections, require regular access to health care facilities and disposal facilities for sharps. Consequently, this proof of concept study was developed to evaluate the use of dissolving microarray patches (MAPs) containing a long-acting (LA) nanosuspension of the candidate ARV drug, rilpivirine (RPV). MAPs were mechanically strong and penetrated skin in vitro, delivering RPV intradermally. In in vivo studies, the mean plasma concentration of RPV in rats (431 ng/ml at the Day 7 time point) was approximately ten-fold greater than the trough concentration observed after a single-dose in previous clinical studies. These results are the first to indicate, by the determination of relative exposures between IM and MAP administration, that larger multi-array dissolving MAPs could potentially be used to effectively deliver human doses of RPV LA. Importantly, RPV was also detected in the lymph nodes, indicating the potential to deliver this ARV agent into one of the primary sites of HIV replication over extended durations. These MAPs could potentially improve patient acceptability and adherence to HIV prevention and treatment regimens and combat instances of needle-stick injury and the transmission of blood-borne diseases, which would have far-reaching benefits, particularly to those in the developing world.

Highlights

Antiretroviral (ARV) drugs have significantly decreased human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) related mortality and morbidity [1]
Given the current study evaluated single-dose RPV LA microarray patch (MAP) and RPV LA IM, the exposure achieved after single-dose administration of RPV LA IM in humans was selected rather than trough concentrations achieved at steady-state
Previous studies have suggested that dissolving MAPs are capable of delivering the cargo located in the needle tips and, in some instances, drug in the baseplate [29]

Summary

Introduction

Antiretroviral (ARV) drugs have significantly decreased human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) related mortality and morbidity [1]. Women are increasingly bearing a disproportionate burden of the AIDS epidemic [2,3]. One means of addressing this burden is through efforts to develop long-acting ARV drug delivery systems for HIV prevention that could be appropriate for use by those at greatest risk of infection. Current guidelines for HIV treatment recommend daily usage of oral ARV drugs but many patients experience treatment fatigue, affecting regimen adherence. The development of long-acting (LA) ARV drugs and delivery systems promises to address and potentially combat these issues surrounding treatment fatigue and poor adherence [4]

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