Novel dissolving bilayer microarray patches as a minimally invasive, efficient intradermal delivery system for a long-acting cabotegravir nanosuspension

Ismaiel Tekko, Lalitkumar Vora, Maeliosa McCrudden, Courtney Jarrahian, Annie Rein-Weston, Darin Zehrung, Paul Giffen, Helen McCarthy, Ryan Donnelly

Research output: Contribution to conferenceOther

Abstract

Introduction:
ViiV Healthcare is developing a long-acting (L A), injectable, nanosuspension of cabotegravir (CAB LA) for both treatment (in combination with rilpivirine LA) and pre-exposure prophylaxis (PrEP) of HIV-1 infection. CAB LA is safe and well-tolerated in humans, but injections can be painful and must be delivered in a clinic, which can limit access in low-resource settings (LRS). , To address this need, we developed minimally invasive microarray patches (MAPs) for intradermal delivery of CAB LA for (PrEP) of HIV-1 infection.

Methods:
To maximize drug loading capacity, MAP moulds, consisted of 16x16 projections (850 µm in height) with cuboidal bodies and pyramidal tips were designed and manufactured. The total area of each array was 0.5 cm2. The moulds were used to fabricate novel, dissolving bi-layer MAPs, with a drug-free base (250 µm in height) made of 35% w/w of (PVA 31-50kDa: PVP K29-32, 1.5:2 w/w) hydrogel and drug-loaded tips (600 µm in height) made of 40% w/w of (PVA 9-10kDa: PVP K29-32, 1:1 w/w) hydrogel with CAB LA nanosuspension (Figure 1). GRAS polymers did not alter CAB LA particle size. MAPs were characterized for mechanical strength, insertion ability, drug deposition, and dissolution kinetics. We measured plasma concentration of CAB LA over time in vivo following a single dose delivered to rats by IM injection, intradermal (ID) injection or MAP.

Results:
We successfully developed novel bilayer MAPs with pyramidal tips containing a remarkably high CAB LA loading (60% w/w) . MAP projections were strong enough to pierce Parafilm® and excised porcine skin models using finger pressure (~17N) and could withstand up to 32N of applied compression force. MAPs submerged in 20 mL PBS solution fully dissolved within 25 minutes and were stable over three months under accelerated conditions. In vivo, CAB LA was detected in blood within 1 hour and reached peak concentration after 9 days. Although plasma concentrations of CAB LA following a single dose delivered by MAP is lower than ID and IM injections, yet they were maintained above therapeutic concentrations of 4xIC90 (664 ng/mL) throughout the 28 day experiment (Figure 2).

Conclusions:
CAB LA MAPs could provide a minimally invasive, needle-free, alternative ID drug delivery system for self-administered HIV PrEP, thereby improving patient acceptability and adherence with particular relevance in low-resource settings.

Acknowledgments: This project is made possible by the generous support of the American people through the United States Agency for International Development (USAID) through the United States President’s Emergency Plan for AIDS Relief (PEPFAR), under the terms of Cooperative Agreement #AID-OAA-A-17-00015. The contents are the responsibility of PATH and do not necessarily reflect the views of USAID, PEPFAR, or the United States government.
Original languageEnglish
Publication statusPublished - 21 Jul 2019
Eventhe 2019 Controlled Release Society Annual Meeting & Exposition - Valencia, Spain
Duration: 21 Jul 201924 Jul 2019
https://2019.controlledreleasesociety.org/

Conference

Conferencehe 2019 Controlled Release Society Annual Meeting & Exposition
Abbreviated titleCRS
CountrySpain
CityValencia
Period21/07/201924/07/2019
Internet address

Keywords

  • Long-acting, Cabotegravir, Microneedles

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Tekko, I., Vora, L., McCrudden, M., Jarrahian, C., Rein-Weston, A., Zehrung, D., Giffen, P., McCarthy, H., & Donnelly, R. (2019). Novel dissolving bilayer microarray patches as a minimally invasive, efficient intradermal delivery system for a long-acting cabotegravir nanosuspension. he 2019 Controlled Release Society Annual Meeting & Exposition, Valencia, Spain.