Injectable Long-acting Human Immunodeficiency Virus Antiretroviral Prodrugs with Improved Pharmacokinetic Profiles

Publication date: Available online 8 October 2018Source: International Journal of PharmaceuticsAuthor(s): Sai Archana Krovi, Matthew D. Gallovic, Austin M. Keller, Menakshi Bhat, Pamela Tiet, Naihan Chen, Michael A. Collier, Elizabeth G. Gurysh, Erica N. Pino, Monica M. Johnson, M. Shamim Hasan Zahid, Mackenzie L. Cottrell, Jason R. Pirone, Angela D. Kashuba, Jesse J. Kwiek, Eric M. Bachelder, Kristy M. AinslieAbstractWhile highly active antiretroviral therapy (HAART) has significantly reduced mortality rates in patients with human immunodeficiency virus type 1 (HIV-1), its efficacy may be impeded by emergence of drug resistance caused by lack of patient adherence. A therapeutic strategy that requires infrequent drug administration as a result of sustained release of antiretroviral drugs would put less burden on the patient. Long-acting antiretroviral prodrugs for HIV therapy were synthesized through modification of the active drugs, emtricitabine (FTC) and elvitegravir (EVG), with docosahexaenoic acid (DHA) in one-step, one-pot, high-yielding reactions. The in vitro drug release profiles of these synthetic conjugates demonstrated sustained and controlled release of the active drug over a period of 3-4 weeks attributable to the hydrolysis of the chemical linker in conjunction with the hydrophilicity of the parent drug. Both conjugates exhibited superior antiviral activities in tissue culture models of HIV replication as compared to those of the free drugs, strengthening their...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research