Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues

Bhavesh D. Kevadiya, Brendan Ottemann, Insiya Z. Mukadam, Laura Castellanos, Kristen Sikora, James R. Hilaire, Jatin Machhi, Jonathan Herskovitz, Dhruvkumar Soni, Mahmudul Hasan, Wenting Zhang, Sarella Anandakumar, Jered Garrison, Jo Ellyn McMillan, Benson Edagwa, R. Lee Mosley, Richard W. Vachet, Howard E. Gendelman

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Human immunodeficiency virus theranostics facilitates the development of long acting (LA) antiretroviral drugs (ARVs) by defining drug-particle cell depots. Optimal drug formulations are made possible based on precise particle composition, structure, shape and size. Through the creation of rod-shaped particles of defined sizes reflective of native LA drugs, theranostic probes can be deployed to measure particle-cell and tissue biodistribution, antiretroviral activities and drug retention. Methods: Herein, we created multimodal rilpivirine (RPV) 177lutetium labeled bismuth sulfide nanorods (177LuBSNRs) then evaluated their structure, morphology, configuration, chemical composition, biological responses and adverse reactions. Particle biodistribution was analyzed by single photon emission computed tomography (SPECT/CT) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging. Results: Nanoformulated RPV and BSNRs-RPV particles showed comparable physicochemical and cell biological properties. Drug-particle pharmacokinetics (PK) and biodistribution in lymphoid tissue macrophages proved equivalent, one with the other. Rapid particle uptake and tissue distribution were observed, without adverse reactions, in primary blood-derived and tissue macrophages. The latter was seen within the marginal zones of spleen. Conclusions: These data, taken together, support the use of 177LuBSNRs as theranostic probes as a rapid assessment tool for PK LA ARV measurements.

Original languageEnglish (US)
Pages (from-to)630-656
Number of pages27
JournalTheranostics
Volume10
Issue number2
DOIs
StatePublished - 2020

Keywords

  • Drug biodistribution
  • Laser ablation inductively coupled plasma mass spectrometry
  • Long acting antiretroviral therapy
  • Multimodal imaging
  • Single photon emission computed tomography

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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