fr
Article scientifique
Accès libre
Anglais

Vaginal rings with exposed cores for sustained delivery of the HIV CCR5 inhibitor 5P12-RANTES

Publié dansJournal of Controlled Release, vol. 298, p. 1-11
Date de publication2019
Résumé

Antiretroviral-releasing vaginal rings are at the forefront of ongoing efforts to develop microbicide-based strategies for prevention of heterosexual transmission of the human immunodeficiency virus (HIV). However, traditional ring designs are generally only useful for vaginal administration of relatively potent, lipophilic, and small molecular weight drug molecules that have sufficient permeability in the non-biodegradable silicone elastomer or thermoplastic polymers. Here, we report a novel, easy-to-manufacture 'exposed-core' vaginal ring that provides sustained release of the protein microbicide candidate 5P12-RANTES, an experimental chemokine analogue that potently blocks the HIV CCR5 coreceptor. In vitro release, mechanical, and stability testing demonstrated the utility and practicality of this novel ring design. In a sheep pharmacokinetic model, a ring containing two ¼-length excipient-modified silicone elastomer cores - each containing lyophilised 5P12-RANTES and exposed to the external environment by two large windows - provided sustained concentrations of 5P12-RANTES in vaginal fluid and vaginal tissue between 10 and 10,000 ng/g over 28days, at least 50 and up to 50,000 times the reported in vitro IC50 value.

Mots-clés
  • Administration
  • Intravaginal
  • Animals
  • Anti-HIV Agents/administration & dosage/pharmacokinetics
  • CCR5 Receptor Antagonists/administration & dosage/pharmacokinetics
  • Chemokines
  • CC/administration & dosage/pharmacokinetics
  • Contraceptive Devices
  • Female
  • Delayed-Action Preparations
  • Drug Delivery Systems
  • Female
  • HIV Infections/prevention & control
  • Humans
  • Inhibitory Concentration 50
  • Sheep
Groupe de recherche
Citation (format ISO)
MCBRIDE, John W et al. Vaginal rings with exposed cores for sustained delivery of the HIV CCR5 inhibitor 5P12-RANTES. In: Journal of Controlled Release, 2019, vol. 298, p. 1–11. doi: 10.1016/j.jconrel.2019.02.003
Fichiers principaux (1)
Article (Published version)
Identifiants
ISSN du journal0168-3659
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Informations techniques

Création17/11/2020 21:49:00
Première validation17/11/2020 21:49:00
Heure de mise à jour15/03/2023 23:23:24
Changement de statut15/03/2023 23:23:23
Dernière indexation12/02/2024 11:58:28
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