Modulating cellular autophagy for controlled antiretroviral drug release

Midhun B. Thomas, Divya Prakash Gnanadhas, Prasanta K. Dash, Jatin Machhi, Zhiyi Lin, JoEllyn M McMillan, Benson J Edagwa, Harris Gelbard, Howard Eliot Gendelman, Santhi Gorantla

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aim: Pharmacologic agents that affect autophagy were tested for their abilities to enhance macrophage nanoformulated antiretroviral drug (ARV) depots and its slow release. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2139-2154
Number of pages16
JournalNanomedicine
Volume13
Issue number17
DOIs
StatePublished - Sep 1 2018

Fingerprint

Autophagy
Macrophages
Pharmaceutical Preparations
Clonidine
Sirolimus
Nanoparticles
Cyclodextrins
Nanocrystals
Metformin
URMC-099
Drug Liberation
Atazanavir Sulfate

Keywords

  • 2-hydroxy-β-cyclodextrin (HBC)
  • URMC-099
  • autophagy
  • clonidine
  • desmethylclomipramine (DMC)
  • long acting slow effective release antiretroviral therapy
  • metformin
  • monocyte-derived macrophages
  • rapamycin

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

Cite this

Modulating cellular autophagy for controlled antiretroviral drug release. / Thomas, Midhun B.; Gnanadhas, Divya Prakash; Dash, Prasanta K.; Machhi, Jatin; Lin, Zhiyi; McMillan, JoEllyn M; Edagwa, Benson J; Gelbard, Harris; Gendelman, Howard Eliot; Gorantla, Santhi.

In: Nanomedicine, Vol. 13, No. 17, 01.09.2018, p. 2139-2154.

Research output: Contribution to journalArticle

Thomas MB, Gnanadhas DP, Dash PK, Machhi J, Lin Z, McMillan JM et al. Modulating cellular autophagy for controlled antiretroviral drug release. Nanomedicine. 2018 Sep 1;13(17):2139-2154. https://doi.org/10.2217/nnm-2018-0224
Thomas, Midhun B. ; Gnanadhas, Divya Prakash ; Dash, Prasanta K. ; Machhi, Jatin ; Lin, Zhiyi ; McMillan, JoEllyn M ; Edagwa, Benson J ; Gelbard, Harris ; Gendelman, Howard Eliot ; Gorantla, Santhi. / Modulating cellular autophagy for controlled antiretroviral drug release. In: Nanomedicine. 2018 ; Vol. 13, No. 17. pp. 2139-2154.
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