Abstract
Antiretroviral (ARV) drugs have, for many years, been studied and administered in the prevention and treatment of human immunodeficiency virus (HIV). Intramuscular (IM) injection of long acting (LA) ARVs are in clinical development, but injectable formulations require regular access to healthcare facilities and disposal facilities for sharps. The development of a discrete, self-administered, and self-disabling vehicle to deliver ARVs could obviate these issues. This study describes the formulation, mechanical characterization, and in vivo evaluation of dissolving microarray patches (MAPs) containing a LA nanosuspension of the ARV, rilpivirine (RPV, RPV LA), for vaginal delivery. This is the first study to apply MAPs into vaginal tissue. The RPV LA MAPs penetrate ex vivo skin and a synthetic vaginal skin model and withstand the effects of potential dragging motion across synthetic vaginal epithelium. In in vivo studies, the mean plasma concentration of RPV in rats at the 56 day endpoint (116.5 ng mL-1 ) is comparable to that achieved in the IM control cohort (118.9 ng mL-1 ). RPV is detected systemically, in lymph and vaginal tissue, indicating the potential to deliver RPV LA to primary sites of viral challenge and replication. This innovative research has future potential for patients and healthcare workers, particularly in low-resource settings.
Highlights
microarray patches (MAPs) utilized in the vaginal delivery of RPV long acting (LA) could eliminate the need for trained specialist administration of the drug, sharps disposal, and the complications associated with needle stick injuries
The research collates the views of potential device end-users on MAP devices and applicators for vaginal delivery of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP)
The outcomes of in vivo experiments determined that RPV LA was detected in plasma, lymph nodes and vaginal tissue of rats who received vaginal MAPs, providing proof of concept for vaginal delivery
Summary
Ethical permission for all in vivo experiments was obtained from the Queen’s University Belfast, Biological Services Unit (BSU) and all researchers carrying out the work held Personal Licenses from the UK Home Office. MAP delivery of RPV LA, compared to IM delivery of RPV LA as a positive control, was assessed in vivo[11] using female Sprague Dawley rats aged between 9 and weeks upon commencement of each arm of the study and between and 17 weeks upon completion of the study. Ethical permission for the experiments was obtained from the Queen’s University Belfast, Biological Services Unit (BSU) and all researchers carrying out the work held Personal Licenses from the UK Home Office. Prior to the commencement of experimentation, rats were acclimatized to laboratory conditions for seven days.
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