Novel Bilayer Microarray Patch‐Assisted Long‐Acting Micro‐Depot Cabotegravir Intradermal Delivery for HIV Pre‐Exposure Prophylaxis

Ismaiel A. Tekko; Lalitkumar K. Vora; Fabiana Volpe-Zanutto; Kurtis Moffatt; Courtney Jarrahian; Helen O. McCarthy; Ryan F. Donnelly

doi:10.1002/adfm.202106999

Novel Bilayer Microarray Patch‐Assisted Long‐Acting Micro‐Depot Cabotegravir Intradermal Delivery for HIV Pre‐Exposure Prophylaxis

Ismaiel A. Tekko, Lalitkumar K. Vora, Fabiana Volpe-Zanutto, Kurtis Moffatt, Courtney Jarrahian, Helen O. McCarthy, Ryan F. Donnelly^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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Abstract

Injectable long-acting cabotegravir (CAB LA) is effective and safe for pre-exposure HIV prophylaxis. It is recently approved for clinical use in those at high risk of contracting HIV. However, injections are invasive and access to trained healthcare personnel to administer CAB LA can be limited, especially in low-income countries (LICs). Herein, for the first time, the development of a bilayer microarray patch (MAP) with unique design and novel formulation as a potential alternative self-administrated intradermal delivery system for CAB is reported. The novel MAP has a high drug load (≈3 mg/0.5 cm² of CAB LA or its micronized sodium salt) and fast-dissolving tips (<30 min) and shows good mechanical properties and skin insertion capabilities. Importantly, in preclinical in vivo studies using Sprague Dawley rats, this MAP is able to implant the drug-loaded tips in the skin, forming micro-depots. Both drug forms are then released in a sustained manner, maintaining human therapeutic levels in the rats for one month after a single application. Weekly repeated MAP dosing in the rats showed the MAPs to be reproducible and well-tolerated. This bilayer MAP presents a promising minimally-invasive, self-administered, alternative delivery system for CAB for enhanced HIV prevention, especially in LICs.

Original language	English
Article number	2106999
Number of pages	18
Journal	Advanced Functional Materials
Early online date	27 Oct 2021
DOIs	https://doi.org/10.1002/adfm.202106999
Publication status	Early online date - 27 Oct 2021

Bibliographical note

Funding Information:
I.A.T. and L.K.V. contributed equally to the work. Thanks to ViiV Healthcare for supplying CAB LA injectable formulation, the micronized cabotegravir sodium and cabotegravir free acid. Thanks to Stephen Lloyd from the Biological Services Unit at Queen's University Belfast for his help while performing the in vivo studies. The authors would also like to thank the PATH team members who contributed to the strategic direction of this work and/or provided review and copyediting support, including Abra Greene, Maggie Kilbourne‐Brook, Annie Rein‐Weston, Jill Sherman‐Konkle, and Darin Zehrung. This project was 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 QUB and PATH and do not necessarily reflect the views of USAID, PEPFAR, or the United States government. Also, this work was supported in part by EPSRC grant EP/S028919/1 and Wellcome Trust grant WT094085MA.

Publisher Copyright:
© 2021 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH

Keywords

Biomaterials
Condensed Matter Physics
Electrochemistry
Electronic, Optical and Magnetic Materials

ASJC Scopus subject areas

Chemistry(all)
Materials Science(all)
Condensed Matter Physics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Novel Bilayer Microarray Patch-Assisted Long-Acting Micro-Depot Cabotegravir Intradermal Delivery for HIV Pre-Exposure Prophylaxis
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 9.45 MBLicence: CC BY

Cite this

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title = "Novel Bilayer Microarray Patch‐Assisted Long‐Acting Micro‐Depot Cabotegravir Intradermal Delivery for HIV Pre‐Exposure Prophylaxis",

abstract = "Injectable long-acting cabotegravir (CAB LA) is effective and safe for pre-exposure HIV prophylaxis. It is recently approved for clinical use in those at high risk of contracting HIV. However, injections are invasive and access to trained healthcare personnel to administer CAB LA can be limited, especially in low-income countries (LICs). Herein, for the first time, the development of a bilayer microarray patch (MAP) with unique design and novel formulation as a potential alternative self-administrated intradermal delivery system for CAB is reported. The novel MAP has a high drug load (≈3 mg/0.5 cm2 of CAB LA or its micronized sodium salt) and fast-dissolving tips (<30 min) and shows good mechanical properties and skin insertion capabilities. Importantly, in preclinical in vivo studies using Sprague Dawley rats, this MAP is able to implant the drug-loaded tips in the skin, forming micro-depots. Both drug forms are then released in a sustained manner, maintaining human therapeutic levels in the rats for one month after a single application. Weekly repeated MAP dosing in the rats showed the MAPs to be reproducible and well-tolerated. This bilayer MAP presents a promising minimally-invasive, self-administered, alternative delivery system for CAB for enhanced HIV prevention, especially in LICs.",

keywords = "Biomaterials, Condensed Matter Physics, Electrochemistry, Electronic, Optical and Magnetic Materials",

author = "Tekko, {Ismaiel A.} and Vora, {Lalitkumar K.} and Fabiana Volpe-Zanutto and Kurtis Moffatt and Courtney Jarrahian and McCarthy, {Helen O.} and Donnelly, {Ryan F.}",

note = "Funding Information: I.A.T. and L.K.V. contributed equally to the work. Thanks to ViiV Healthcare for supplying CAB LA injectable formulation, the micronized cabotegravir sodium and cabotegravir free acid. Thanks to Stephen Lloyd from the Biological Services Unit at Queen's University Belfast for his help while performing the in vivo studies. The authors would also like to thank the PATH team members who contributed to the strategic direction of this work and/or provided review and copyediting support, including Abra Greene, Maggie Kilbourne‐Brook, Annie Rein‐Weston, Jill Sherman‐Konkle, and Darin Zehrung. This project was 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 QUB and PATH and do not necessarily reflect the views of USAID, PEPFAR, or the United States government. Also, this work was supported in part by EPSRC grant EP/S028919/1 and Wellcome Trust grant WT094085MA. Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH",

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language = "English",

journal = "Advanced Functional Materials",

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Novel Bilayer Microarray Patch‐Assisted Long‐Acting Micro‐Depot Cabotegravir Intradermal Delivery for HIV Pre‐Exposure Prophylaxis. / Tekko, Ismaiel A.; Vora, Lalitkumar K.; Volpe-Zanutto, Fabiana; Moffatt, Kurtis; Jarrahian, Courtney; McCarthy, Helen O.; Donnelly, Ryan F.

In: Advanced Functional Materials, 27.10.2021.

Research output: Contribution to journal › Article › peer-review

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T1 - Novel Bilayer Microarray Patch‐Assisted Long‐Acting Micro‐Depot Cabotegravir Intradermal Delivery for HIV Pre‐Exposure Prophylaxis

AU - Tekko, Ismaiel A.

AU - Vora, Lalitkumar K.

AU - Volpe-Zanutto, Fabiana

AU - Moffatt, Kurtis

AU - Jarrahian, Courtney

AU - McCarthy, Helen O.

AU - Donnelly, Ryan F.

N1 - Funding Information: I.A.T. and L.K.V. contributed equally to the work. Thanks to ViiV Healthcare for supplying CAB LA injectable formulation, the micronized cabotegravir sodium and cabotegravir free acid. Thanks to Stephen Lloyd from the Biological Services Unit at Queen's University Belfast for his help while performing the in vivo studies. The authors would also like to thank the PATH team members who contributed to the strategic direction of this work and/or provided review and copyediting support, including Abra Greene, Maggie Kilbourne‐Brook, Annie Rein‐Weston, Jill Sherman‐Konkle, and Darin Zehrung. This project was 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 QUB and PATH and do not necessarily reflect the views of USAID, PEPFAR, or the United States government. Also, this work was supported in part by EPSRC grant EP/S028919/1 and Wellcome Trust grant WT094085MA. Publisher Copyright: © 2021 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH

PY - 2021/10/27

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N2 - Injectable long-acting cabotegravir (CAB LA) is effective and safe for pre-exposure HIV prophylaxis. It is recently approved for clinical use in those at high risk of contracting HIV. However, injections are invasive and access to trained healthcare personnel to administer CAB LA can be limited, especially in low-income countries (LICs). Herein, for the first time, the development of a bilayer microarray patch (MAP) with unique design and novel formulation as a potential alternative self-administrated intradermal delivery system for CAB is reported. The novel MAP has a high drug load (≈3 mg/0.5 cm2 of CAB LA or its micronized sodium salt) and fast-dissolving tips (<30 min) and shows good mechanical properties and skin insertion capabilities. Importantly, in preclinical in vivo studies using Sprague Dawley rats, this MAP is able to implant the drug-loaded tips in the skin, forming micro-depots. Both drug forms are then released in a sustained manner, maintaining human therapeutic levels in the rats for one month after a single application. Weekly repeated MAP dosing in the rats showed the MAPs to be reproducible and well-tolerated. This bilayer MAP presents a promising minimally-invasive, self-administered, alternative delivery system for CAB for enhanced HIV prevention, especially in LICs.

AB - Injectable long-acting cabotegravir (CAB LA) is effective and safe for pre-exposure HIV prophylaxis. It is recently approved for clinical use in those at high risk of contracting HIV. However, injections are invasive and access to trained healthcare personnel to administer CAB LA can be limited, especially in low-income countries (LICs). Herein, for the first time, the development of a bilayer microarray patch (MAP) with unique design and novel formulation as a potential alternative self-administrated intradermal delivery system for CAB is reported. The novel MAP has a high drug load (≈3 mg/0.5 cm2 of CAB LA or its micronized sodium salt) and fast-dissolving tips (<30 min) and shows good mechanical properties and skin insertion capabilities. Importantly, in preclinical in vivo studies using Sprague Dawley rats, this MAP is able to implant the drug-loaded tips in the skin, forming micro-depots. Both drug forms are then released in a sustained manner, maintaining human therapeutic levels in the rats for one month after a single application. Weekly repeated MAP dosing in the rats showed the MAPs to be reproducible and well-tolerated. This bilayer MAP presents a promising minimally-invasive, self-administered, alternative delivery system for CAB for enhanced HIV prevention, especially in LICs.

KW - Biomaterials

KW - Condensed Matter Physics

KW - Electrochemistry

KW - Electronic, Optical and Magnetic Materials

U2 - 10.1002/adfm.202106999

DO - 10.1002/adfm.202106999

M3 - Article

AN - SCOPUS:85118200620

JO - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-3028

M1 - 2106999

ER -

Novel Bilayer Microarray Patch‐Assisted Long‐Acting Micro‐Depot Cabotegravir Intradermal Delivery for HIV Pre‐Exposure Prophylaxis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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