Theranostics 2020; 10(2):630-656. doi:10.7150/thno.39847
Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues
1. Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, NE, USA
2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, NE, USA
3. Department of Chemistry, University of Massachusetts, Amherst, MA, USA
4. Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, NE, USA
5. Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, NE, USA
Kevadiya BD, Ottemann B, Mukadam IZ, Castellanos L, Sikora K, Hilaire JR, Machhi J, Herskovitz J, Soni D, Hasan M, Zhang W, Anandakumar S, Garrison J, McMillan J, Edagwa B, Mosley RL, Vachet RW, Gendelman HE. Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues. Theranostics 2020; 10(2):630-656. doi:10.7150/thno.39847. Available from http://www.thno.org/v10p0630.htm
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.
Keywords: Long acting antiretroviral therapy, Laser ablation inductively coupled plasma mass spectrometry, Single photon emission computed tomography, Drug biodistribution, Multimodal imaging