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 language | English (US) |
|---|---|
| Pages (from-to) | 658-668 |
| Number of pages | 11 |
| Journal | Journal of Controlled Release |
| Volume | 330 |
| DOIs | |
| State | Published - Feb 10 2021 |
Funding
We are grateful to Viiv Healthcare Ltd. for providing cabotegravir to the project. We especially thank Alex Rinehart, Ph.D., William R. Spreen, Pharm.D. from ViiV Healthcare Ltd, and Meredith Clark, Ph.D., from CONRAD for their collective input on this work. Mark Marzinke, Ph.D., from Johns Hopkins University and Meagan Watkins from Tulane University assisted with bioanalytical measurements and the non-human primate studies respectively. We thank Alicia Potuck, Ph.D., from ViiV Healthcare Ltd, for helpful comments on the manuscript. We recognize the use of the IMSERC X-ray Facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource ( NSF ECCS-1542205 ); the State of Illinois and International Institute for Nanotechnology (IIN) . Funding for this work was provided by NIH NIAID grant UM1 AI120184. We are grateful to Viiv Healthcare Ltd. for providing cabotegravir to the project. We especially thank Alex Rinehart, Ph.D. William R. Spreen, Pharm.D. from ViiV Healthcare Ltd, and Meredith Clark, Ph.D. from CONRAD for their collective input on this work. Mark Marzinke, Ph.D. from Johns Hopkins University and Meagan Watkins from Tulane University assisted with bioanalytical measurements and the non-human primate studies respectively. We thank Alicia Potuck, Ph.D. from ViiV Healthcare Ltd, for helpful comments on the manuscript. We recognize the use of the IMSERC X-ray Facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the State of Illinois and International Institute for Nanotechnology (IIN). Funding for this work was provided by NIH NIAID grant UM1 AI120184.
Keywords
- Cabotegravir
- Hot-melt extrusion
- Hydrophilic poly(ether urethane)
- Pre-exposure prophylaxis
- Reservoir device
- Subcutaneous implant
ASJC Scopus subject areas
- Pharmaceutical Science
