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A long acting nanoformulated lamivudine ProTide
Nathan Smith1, Aditya N Bade1, Dhruvkumar Soni2
1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Biomaterials
|September 17, 2019
Summary
A novel long-acting lamivudine prodrug (M23TC) and its nanoformulation (NM23TC) show improved antiretroviral activity and sustained drug levels. This offers a promising advancement for developing slow-release antiretroviral therapies.
Area of Science:
- Pharmacology
- Drug Delivery
- Virology
Background:
- Lamivudine (3TC) is a key antiretroviral drug.
- Improving its pharmacokinetic (PK) and intracellular delivery is crucial for enhanced efficacy.
- Developing long-acting (LA) formulations can improve patient adherence and treatment outcomes.
Purpose of the Study:
- To create a long-acting, hydrophobic, and lipophilic lamivudine prodrug (M23TC).
- To evaluate the efficacy of nanoformulated M23TC (NM23TC) in vitro and in vivo.
- To assess the pharmacokinetic profile of NM23TC for sustained antiretroviral therapy.
Main Methods:
- Synthesis of a phosphoramidate pronucleotide prodrug of lamivudine (M23TC).
- Treatment of human monocyte-derived macrophages (MDM) and CD4+ T cells with nanoformulated M23TC (NM23TC).
- In vivo pharmacokinetic studies in Sprague Dawley rats using NM23TC.
Main Results:
- NM23TC demonstrated improved intracellular delivery of active triphosphate metabolites.
- NM23TC showed enhanced antiretroviral activity in MDM and CD4+ T cells.
- Pharmacokinetic studies revealed sustained prodrug and active metabolite levels in rats for 30 days.
Conclusions:
- Nanoformulated M23TC represents a significant advancement in developing long-acting antiretroviral drugs.
- The improved drug delivery and sustained release profiles of NM23TC hold potential for future clinical translation.
- This approach offers a promising strategy for effective, slow-release antiretroviral therapies.
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