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

K. Moffatt, I.A. Tekko, L. Vora, F. Volpe-Zanutto, A.R.J. Hutton, J. Mistilis, C. Jarrahian, N. Akhavein, A.D. Weber, H.O. McCarthy, R.F. Donnelly

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18 Citations (Scopus)

Abstract

Purpose Whilst signifcant progress has been made to defeat HIV infection, the efcacy 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 profles, 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
Pages (from-to)1673-1696
Number of pages22
JournalPharmaceutical Research
Volume40
Early online date12 Oct 2022
DOIs
Publication statusPublished online - 12 Oct 2022

Keywords

  • AIDS, acquired immune deficiency syndrome
  • CAB, cabotegravir
  • HIV, human immunodefciency virus
  • MAP, microarray patch
  • RPV, rilpivirine

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