Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA; Department of Physics and Engineering, Elon University, Elon, NC, USA.
J Control Release. 2021 Feb 10;330:658-668. doi: 10.1016/j.jconrel.2020.12.024. Epub 2020 Dec 19.
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.
长效抗逆转录病毒植入物可以帮助高风险个体预防 HIV 感染。我们描述了一种长效储库皮下植入物的设计和测试，该植入物能够释放卡替拉韦几个月。我们将卡替拉韦和赋形剂压缩成圆柱形颗粒，并将其热封在由亲水性聚（醚-聚氨酯）-组成的管中。植入物的腔体长 47 毫米，外径 3.6 毫米，壁厚 200 微米。四个卡替拉韦颗粒被密封在膜中，总药物负载为 274±3 毫克。在体内，植入物在恒河猴中每天释放 348±107μg 的卡替拉韦（每个植入物的中位数，N=41）。五个植入物在恒河猴中产生平均卡替拉韦血浆浓度为 373ng/ml。与安慰剂植入物相比，非人类灵长类动物耐受植入物，没有大体病理学或组织病理学的微观迹象。在植入物取出后两周内，猴体内的卡替拉韦血浆水平降至检测不到的水平。
