作者
Tanmay A Kulkarni, Aditya N Bade, Brady Sillman, Bhagya Laxmi Dyavar Shetty, Melinda S Wojtkiewicz, Nagsen Gautam, James R Hilaire, Sruthi Sravanam, Adam Szlachetka, Benjamin G Lamberty, Brenda M Morsey, Howard S Fox, Yazen Alnouti, JoEllyn M McMillan, R Lee Mosley, Jane Meza, Paul L Domanico, Tai-Yuen Yue, Gary Moore, Benson J Edagwa, Howard E Gendelman
发表日期
2020/8
期刊
Nature materials
卷号
19
期号
8
页码范围
910-920
出版商
Nature Publishing Group UK
简介
Long-acting cabotegravir (CAB) extends antiretroviral drug administration from daily to monthly. However, dosing volumes, injection site reactions and health-care oversight are obstacles towards a broad usage. The creation of poloxamer-coated hydrophobic and lipophilic CAB prodrugs with controlled hydrolysis and tissue penetrance can overcome these obstacles. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18 and 22 added carbon chains were encased in biocompatible surfactants named NMCAB, NM2CAB and NM3CAB and tested for drug release, activation, cytotoxicity, antiretroviral activities, pharmacokinetics and biodistribution. Pharmacokinetics studies, performed in mice and rhesus macaques, with the lead 18-carbon ester chain NM2CAB, showed plasma CAB levels above the protein-adjusted 90% inhibitory concentration for up to a year. NM2CAB, compared with NMCAB and …
学术搜索中的文章
TA Kulkarni, AN Bade, B Sillman, BLD Shetty… - Nature materials, 2020