Sustained Intracellular Raltegravir Depots Generated with Prodrugs Designed for Nanoparticle Delivery.

ABSTRACT: Polymeric nanocarriers have been extensively used to improve the delivery of hydrophobic drugs, but often provide low encapsulation efficiency and percent loading for hydrophilic compounds. In particular, insufficient loading of hydrophilic antiretroviral drugs such as the integrase inhibitor raltegravir (RAL) has limited the development of sustained-release therapeutics or prevention strategies against HIV. To address this, we developed a generalizable prodrug strategy using RAL as a model where loading, release and subsequent hydrolysis can be tuned by promoiety selection. Prodrugs with large partition coefficients increased the encapsulation efficiency up to 25-fold relative to RAL, leading to significant dose reductions in antiviral activity assays. The differential hydrolysis rates of

SUBMITTER: Creighton RL 

PROVIDER: S-EPMC7591136 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature