Design and Testing of a Cabotegravir Implant for HIV Prevention.

Animals Anti-HIV Agents / therapeutic use HIV Infections / drug therapy HIV-1 Macaca mulatta Pyridones
Cabotegravir Hot-melt extrusion Hydrophilic poly(ether urethane) Pre-exposure prophylaxis Reservoir device Subcutaneous implant

Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
10 02 2021
Historique:
received: 24 06 2020
revised: 14 12 2020
accepted: 15 12 2020
pubmed: 22 12 2020
medline: 8 7 2021
entrez: 21 12 2020
Statut: ppublish

Résumé

Long-acting antiretroviral implants could help protect high-risk individuals from HIV infection. We describe the design and testing of a long-acting reservoir subcutaneous implant capable of releasing cabotegravir for several months. We compressed cabotegravir and excipients into cylindrical pellets and heat-sealed them in tubing composed of hydrophilic poly(ether-urethane) -. The implants have a 47 mm lumen length, 3.6 mm outer diameter, and 200 μm wall thickness. Four cabotegravir pellets were sealed in the membrane, with a total drug loading of 274 ± 3 mg. In vivo, the implants released 348 ± 107 μg/day (median value per implant, N = 41) of cabotegravir in rhesus macaques. Five implants generated an average cabotegravir plasma concentration of 373 ng/ml in rhesus macaques. The non-human primates tolerated the implant without gross pathology or microscopic signs of histopathology compared to placebo implants. Cabotegravir plasma levels in macaques dropped below detectable levels within two weeks after the removal of the implants.

Identifiants

DOI: 10.1016/j.jconrel.2020.12.024 PMID: 33347943 PMC: PMC7906957
pubmed: 33347943
pii: S0168-3659(20)30748-3
doi: 10.1016/j.jconrel.2020.12.024
pmc: PMC7906957
mid: NIHMS1661893
pii:
doi:

Substances chimiques

Anti-HIV Agents 0
Pyridones 0
cabotegravir HMH0132Z1Q

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

658-668

Subventions

Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI131433
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI120184
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Références

Pharm Res. 1998 Jun;15(6):889-96
pubmed: 9647355
Lancet Infect Dis. 2020 Jul;20(7):781
pubmed: 32592669
HIV AIDS (Auckl). 2015 Oct 13;7:241-9
pubmed: 26508889
J Control Release. 2018 Sep 28;286:315-325
pubmed: 30092254
Lancet. 2017 Sep 23;390(10101):1499-1510
pubmed: 28750935
Antimicrob Agents Chemother. 2012 Dec;56(12):6272-83
pubmed: 23006751
Antimicrob Agents Chemother. 2018 Sep 24;62(10):
pubmed: 30012772
Contraception. 2011 May;83(5):397-404
pubmed: 21477680
Sci Transl Med. 2015 Jan 14;7(270):270ra4
pubmed: 25589630
Lancet HIV. 2020 Mar;7(3):e164-e172
pubmed: 31911147
Antimicrob Agents Chemother. 2020 Feb 21;64(3):
pubmed: 31871073
Annu Rev Med. 2019 Jan 27;70:137-150
pubmed: 30355266
J Acquir Immune Defic Syndr. 2014 Dec 15;67(5):481-6
pubmed: 25140909
Pharmaceutics. 2018 May 09;10(2):
pubmed: 29747409
Curr Opin HIV AIDS. 2015 Jul;10(4):246-52
pubmed: 26049949
Curr Opin HIV AIDS. 2015 Jul;10(4):258-63
pubmed: 26049951
JAMA. 2019 Mar 5;321(9):844-845
pubmed: 30730529
HIV Clin Trials. 2013 Sep-Oct;14(5):192-203
pubmed: 24144896
J Control Release. 2019 Jul 28;306:89-96
pubmed: 31136811
Eur J Drug Metab Pharmacokinet. 2019 Jun;44(3):319-327
pubmed: 30387005
J Tissue Eng Regen Med. 2007 Mar-Apr;1(2):110-9
pubmed: 18038399
Pharm Res. 2016 Jul;33(7):1649-56
pubmed: 26975357
Clin Pharmacol Drug Dev. 2019 May;8(4):443-448
pubmed: 30230694
Pharmaceutics. 2019 Jul 04;11(7):
pubmed: 31277461
Expert Rev Clin Pharmacol. 2018 May;11(5):507-517
pubmed: 29595351
J Med Chem. 2013 Jul 25;56(14):5901-16
pubmed: 23845180
Science. 2014 Mar 7;343(6175):1151-4
pubmed: 24594934
BMC Infect Dis. 2018 Nov 16;18(1):581
pubmed: 30445925
AIDS Behav. 2017 May;21(5):1336-1349
pubmed: 27770215
Curr Opin HIV AIDS. 2015 Jul;10(4):239-45
pubmed: 26049948
Curr HIV/AIDS Rep. 2017 Apr;14(2):63-71
pubmed: 28303548
N Engl J Med. 2005 Aug 4;353(5):487-97
pubmed: 16079372
Antimicrob Agents Chemother. 2015 Jan;59(1):397-406
pubmed: 25367908
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Pharm Res. 2020 Apr 15;37(4):83
pubmed: 32296951
Antimicrob Agents Chemother. 2015 Jul;59(7):3913-9
pubmed: 25896688

Auteurs

Dipu Karunakaran (D)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

Solange M Simpson (SM)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

Jonathan T Su (JT)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA; Department of Physics and Engineering, Elon University, Elon, NC, USA.

Ewa Bryndza-Tfaily (E)

Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA.

Thomas J Hope (TJ)

Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA.

Ronald Veazey (R)

Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA.

Georgina Dobek (G)

Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA; Tulane University School of Medicine, New Orleans, LA, USA.

Jiang Qiu (J)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

David Watrous (D)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

Samuel Sung (S)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

Jorge E Chacon (JE)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

Patrick F Kiser (PF)

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA. Electronic address: patrick.kiser@northwestern.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Design and Testing of a Cabotegravir Implant...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Agents antiVIH › Design and Testing of a Cabotegravir Implant...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › Design and Testing of a Cabotegravir Implant...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › Design and Testing of a Cabotegravir Implant...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca › Macaca mulatta › Design and Testing of a Cabotegravir Implant...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Pyridones › Design and Testing of a Cabotegravir Implant...