Design and Testing of a Cabotegravir Implant for HIV Prevention

JOURNAL OF CONTROLLED RELEASE

卷:330

Article

Karunakaran, Dipu¹  Simpson, Solange M.¹  Su, Jonathan T.^1,2  Bryndza-Tfaily, Ewa³  Hope, Thomas J.³  Veazey, Ronald⁴  Dobek, Georgina^4,5  Qiu, Jiang¹  Watrous, David¹  Sung, Samuel¹  Chacon, Jorge E.¹  Kiser, Patrick F.¹ 

[1] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA

[2] Elon Univ, Dept Phys & Engn, Elon, NC USA

[3] Northwestern Univ, Dept Cell & Dev Biol, Chicago, IL 60611 USA

[4] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA USA

[5] Tulane Univ, Sch Med, 1430 Tulane Ave, New Orleans, LA 70112 USA

关键词: Cabotegravir;    Subcutaneous implant;    Pre-exposure prophylaxis;    Hot-melt extrusion;    Hydrophilic poly(ether urethane);    Reservoir device;   

DOI  :  10.1016/j.jconrel.2020.12.024

来源: Elsevier

【 摘 要 】

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 mu m 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 mu g/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.

【 授权许可】

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