Design and Testing of a Cabotegravir Implant for HIV Prevention

Dipu Karunakaran, Solange M. Simpson, Jonathan T. Su, Ewa Bryndza-Tfaily, Thomas J. Hope, Ronald Veazey, Georgina Dobek, Jiang Qiu, David Watrous, Samuel Sung, Jorge E. Chacon, Patrick F. Kiser*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)658-668
Number of pages11
JournalJournal of Controlled Release
Volume330
DOIs
StatePublished - Feb 10 2021

Keywords

  • Cabotegravir
  • Hot-melt extrusion
  • Hydrophilic poly(ether urethane)
  • Pre-exposure prophylaxis
  • Reservoir device
  • Subcutaneous implant

ASJC Scopus subject areas

  • Pharmaceutical Science

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