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Modulating cellular autophagy for controlled antiretroviral drug release.

Authors
  • Thomas, Midhun B1
  • Gnanadhas, Divya Prakash1
  • Dash, Prasanta K1
  • Machhi, Jatin1
  • Lin, Zhiyi1
  • McMillan, JoEllyn1
  • Edagwa, Benson1
  • Gelbard, Harris2
  • Gendelman, Howard E1
  • Gorantla, Santhi1
  • 1 Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Centre, Omaha, NE 68198, USA.
  • 2 Department of Neurology, University of Rochester Medical Centre, Rochester, NY 14618, USA.
Type
Published Article
Journal
Nanomedicine
Publisher
Future Medicine
Publication Date
Sep 01, 2018
Volume
13
Issue
17
Pages
2139–2154
Identifiers
DOI: 10.2217/nnm-2018-0224
PMID: 30129397
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Pharmacologic agents that affect autophagy were tested for their abilities to enhance macrophage nanoformulated antiretroviral drug (ARV) depots and its slow release. These agents included URMC-099, rapamycin, metformin, desmethylclomipramine, 2-hydroxy-β-cyclodextrin (HBC) and clonidine. Each was administered with nanoformulated atazanavir (ATV) nanoparticles to human monocyte-derived macrophages. ARV retention, antiretroviral activity and nanocrystal autophagosomal formation were evaluated. URMC-099, HBC and clonidine retained ATV. HBC, URMC-099 and rapamycin improved intracellular ATV retention. URMC-099 proved superior among the group in affecting antiretroviral activities. Autophagy inducing agents, notably URMC-099, facilitate nanoformulated ARV depots and lead to sustained release and improved antiretroviral responses. As such, they may be considered for development as part of long acting antiretroviral treatment regimens.

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