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

Authors

Bhavesh D. Kevadiya, University of Nebraska Medical Center
Brendan Ottemann, University of Nebraska Medical Center
Insiya Z. Mukadam, University of Nebraska Medical Center
Laura Castellanos, University of Massachusetts Amherst
Kristen Sikora, University of Massachusetts Amherst
James R. Hilaire, University of Nebraska Medical Center
Jatin Machhi, University of Nebraska Medical CenterFollow
Jonathan Herskovitz, University of Nebraska Medical Center
Dhruvkumar Soni, University of Nebraska Medical Center
Mahmudul Hasan, University of Nebraska Medical CenterFollow
Wenting Zhang, University of Nebraska Medical CenterFollow
Anandakumar Sarella, University of Nebraska Medical CenterFollow
Jered Garrison, University of Nebraska Medical CenterFollow
JoEllyn McMillan, University of Nebraska Medical CenterFollow
Benson Edagwa, University of Nebraska Medical CenterFollow
R. Lee Mosley, University of Nebraska Medical CenterFollow
Richard W. Vachet, University of Massachusetts Amherst
Howard E. Gendelman, University of Nebraska Medical CenterFollow

Date of this Version

2020

Citation

Theranostics 2020, Vol. 10, Issue 2

Comments

© The author(s).

Open access

doi: 10.7150/thno.39847

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.