2-Hydroxypropyl-β-cyclodextrin-enhanced pharmacokinetics of cabotegravir from a nanofluidic implant for HIV pre-exposure prophylaxis.

2-Hydroxypropyl-beta-cyclodextrin / administration & dosage Animals Anti-HIV Agents / pharmacokinetics Drug Delivery Systems / adverse effects HIV Infections / prevention & control Male Pre-Exposure Prophylaxis Pyridones / administration & dosage Rats Rats, Sprague-Dawley
Cabotegravir Formulation HIV Implant PrEP

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:
28 07 2019
Historique:
received: 21 03 2019
revised: 14 05 2019
accepted: 23 05 2019
pubmed: 29 5 2019
medline: 15 9 2020
entrez: 29 5 2019
Statut: ppublish

Résumé

Preexposure prophylaxis (PrEP) with antiretrovirals (ARV) can prevent human immunodeficiency virus (HIV) transmission, but its efficacy is highly dependent on strict patient adherence to daily dosing regimen. Long-acting (LA) ARV formulations or delivery systems that reduce dosing frequency may increase adherence and thus PrEP efficacy. While cabotegravir (CAB) long-acting injectable (CAB LA), an integrase strand transfer inhibitor (INSTI), reduces dosing frequency to bimonthly injections, variable pharmacokinetics (PK) between patients and various adverse reactions necessitate improvement in delivery methods. Here we developed a subcutaneously implantable nanofluidic device for the sustained delivery of CAB formulated with 2-hydroxypropyl-β-cyclodextrin (βCAB) and examined the pharmacokinetics (PK) in Sprague-Dawley rats for 3 months in comparison to CAB. Our study demonstrated βCAB treatment group maintained clinically-relevant plasma CAB concentrations 2 times above the protein-adjusted concentration that inhibits viral replication by 90% (2 × PA-IC

Identifiants

DOI: 10.1016/j.jconrel.2019.05.037 PMID: 31136811 PMC: PMC8591786
pubmed: 31136811
pii: S0168-3659(19)30301-3
doi: 10.1016/j.jconrel.2019.05.037
pmc: PMC8591786
mid: NIHMS1750592
pii:
doi:

Substances chimiques

Anti-HIV Agents 0
Pyridones 0
2-Hydroxypropyl-beta-cyclodextrin 1I96OHX6EK
cabotegravir HMH0132Z1Q

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

89-96

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI120749
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

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Auteurs

Fernanda P Pons-Faudoa (FP)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA; Tecnologico de Monterrey, School of Medicine and Health Sciences, Monterrey, NL, Mexico.

Antons Sizovs (A)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.

Nicola Di Trani (N)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA; University of Chinese Academy of Science (UCAS), Beijing, China.

Jesus Paez-Mayorga (J)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA; Tecnologico de Monterrey, School of Medicine and Health Sciences, Monterrey, NL, Mexico.

Giacomo Bruno (G)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA; Politecnico di Torino, Turin, Italy.

Jessica Rhudy (J)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.

Madhuri Manohar (M)

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Kevin Gwenden (K)

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Cecilia Martini (C)

Chemistry and Nanotechnology Unit, Institute of Organic Synthesis and Photoreactivity (IOSP), Bologna, Italy.

Corrine Ying Xuan Chua (CYX)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA.

Greta Varchi (G)

Chemistry and Nanotechnology Unit, Institute of Organic Synthesis and Photoreactivity (IOSP), Bologna, Italy.

Mark A Marzinke (MA)

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Alessandro Grattoni (A)

Department of Nanomedicine, Houston Methodist Research Institute (HMRI), Houston, TX, USA; Department of Surgery, Houston Methodist Hospital, Houston, TX, USA; Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. Electronic address: agrattoni@houstonmethodist.org.

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Classifications MeSH

questionsmedicales.fr › Glucides › Polyosides › Glucanes › Amidon › Dextrine › Cyclodextrines › Cyclodextrines bêta › 2-Hydroxypropyl-beta-cyclodextrin › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Eucaryotes › Animaux › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Agents antiVIH › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Systèmes de délivrance de médicaments › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Prophylaxie pré-exposition › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Pyridones › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › 2-Hydroxypropyl-β-cyclodextrin-enhanced...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › 2-Hydroxypropyl-β-cyclodextrin-enhanced...