Year: 2020
Type: article
Abstract: Nowadays, there is a strong request for the treatment of chronic HBV-infection with direct acting antivirals. Furthermore, prevalent human immunodeficiency virus (HIV-1) and hepatitis B (HBV) co-infections highlight an immediate need for dual long-acting and easily administered antivirals. To this end, we modified lamivudine (3TC), a nucleoside analog inhibitor of both viruses, into a lipophilic monophosphorylated prodrug (M23TC). Prior work demonstrated that nanoformulation of M23TC (NM23TC) enhanced drug stability, controlled dissolution and improved access to sites of viral replication. The present study evaluated the efficacy of a NM23TC in HBV-infected chimeric liver humanized mice. Levels of HBV DNA and HBsAg in plasma were monitored up to 8 weeks posttreatment. A single intramuscular dose of 75 mg/kg 3TC equivalents of nanoformulated NM23TC provided sustained drug levels and suppressed HBV replication in humanized mice for 4 weeks. The results support further development of this long-acting 3TC nanoformulation for HBV treatment and prevention.
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,550
Funders: University of Nebraska Medical Center, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke
Awards: Combined Molecular Excision Therapy (CMET) for Eliminating HIV-1, Center for Humanized Mice, NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence, Ethanol suppresses HBV peptide-MHC Class I presentation on hepatocytes, Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center, Nanomedicine and NeuroAIDS, Dysregulation of metabolic and bioenergetic pathways by cocaine and HIV-1 in CNS, SMART HAND, Chemical, Nanomedicine and Autophagy Strategies to Create Sustained-Release Antiretroviral Products, Neuroprotective Immunity and HIV Dementia, Prodrug Formulations Create Sustained-Release Antiretrovirals, Broad-spectrum HIV gene editing strategies in peripheral and brain reservoirs
OpenAlex ID: W3013866420