Development and evaluation of dissolving microarray patches for co-administered and repeated intradermal delivery of long-acting rilpivirine and cabotegravir nanosuspensions for paediatric HIV antiretroviral therapy

Kurtis Moffatt, Ismaiel A. Tekko, Lalitkumar Vora, Fabiana Volpe-Zanutto, Aaron R. J. Hutton, Jessica Mistilis, Courtney Jarrahian, Nima Akhavein, Andrew D. Weber, Helen O. McCarthy, Ryan F. Donnelly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)
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Abstract

Purpose
Whilst significant progress has been made to defeat HIV infection, the efficacy of antiretroviral (ARV) therapy in the paediatric population is often hindered by poor adherence. Currently, two long-acting (LA) intramuscular injectable nanosuspensions of rilpivirine (RPV) and cabotegravir (CAB) are in clinical development for paediatric populations. However, administration requires access to healthcare resources, is painful, and can result in needle-stick injuries to the end user. To overcome these barriers, this proof-of-concept study was developed to evaluate the intradermal delivery of RPV LA and CAB LA via self-disabling dissolving microarray patches (MAPs).

Methods
Dissolving MAPs of two conformations, a conventional pyramidal and a bilayer design, were formulated, with various nanosuspensions of RPV and CAB incorporated within the respective MAP matrix. MAPs were mechanically robust and were capable of penetrating ex vivo skin with intradermal ARV deposition.

Results
In a single-dose in vivo study in rats, all ARV MAPs demonstrated sustained release profiles, with therapeutically relevant plasma concentrations of RPV and CAB detected to at least 63 and 28 d, respectively. In a multi-dose in vivo study, repeated MAP applications at 14-d intervals maintained therapeutically relevant plasma concentrations throughout the duration of the study.

Conclusions
These results illustrate the potential of the platform to repeatedly maintain plasma concentrations for RPV and CAB. As such, these MAPs could represent a viable option to improve adherence in the paediatric population, one that is capable of being painlessly administered in the comfort of the patient’s own home on a biweekly or less frequent basis.
Original languageEnglish
Number of pages24
JournalPharmaceutical Research
Early online date12 Oct 2022
DOIs
Publication statusEarly online date - 12 Oct 2022

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