TY - JOUR
T1 - Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues
AU - Kevadiya, Bhavesh D.
AU - Ottemann, Brendan
AU - Mukadam, Insiya Z.
AU - Castellanos, Laura
AU - Sikora, Kristen
AU - Hilaire, James R.
AU - Machhi, Jatin
AU - Herskovitz, Jonathan
AU - Soni, Dhruvkumar
AU - Hasan, Mahmudul
AU - Zhang, Wenting
AU - Anandakumar, Sarella
AU - Garrison, Jered
AU - McMillan, Jo Ellyn
AU - Edagwa, Benson
AU - Mosley, R. Lee
AU - Vachet, Richard W.
AU - Gendelman, Howard E.
N1 - Publisher Copyright:
© The author(s).
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Drug biodistribution
KW - Laser ablation inductively coupled plasma mass spectrometry
KW - Long acting antiretroviral therapy
KW - Multimodal imaging
KW - Single photon emission computed tomography
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U2 - 10.7150/thno.39847
DO - 10.7150/thno.39847
M3 - Article
C2 - 31903142
AN - SCOPUS:85076574661
SN - 1838-7640
VL - 10
SP - 630
EP - 656
JO - Theranostics
JF - Theranostics
IS - 2
ER -