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

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.

Comprehensive Review on Current Interventions, Diagnostics, and Nanotechnology Perspectives against SARS-CoV-2

“…Bismuth- and sulfur-containing nanorods intrinsically radiolabeled with luteium 177 ( 177 LuBSNRs) can render both antiviral therapy and multimodal imaging. 224 The gold nanorods combined with the curcumin loaded poly (lactic- co -glycolic acid)- block -poly (ethylene glycol) (PLGA-b-PEG) copolymer are helpful for triggered and localized release of therapeutics along with photothermal capacity in one system. 225 The albumin-Bi 2 S 3 and magnetic nanoparticles can be developed for the combination of radiotherapy, magnetic hyperthermia, and chemotherapy.…”

Europium sulfide nanoprobes predict antiretroviral drug delivery into HIV-1 cell and tissue reservoirs

“…Prior studies have demonstrated high RPV levels in kidney and gut exceeding those of spleen and liver 56 days after intramuscular dosing with poloxamer-encapsulated NRPV 19 . By contrast, intravenous co-dosing of bismuth-sulfate nanorods (BSNRs) with NRPV favored drug deposition in spleen and lymph node rather than kidney by four weeks post-injection 15 . Our findings recapitulate the notion that IV administration of NRPV enhances deposition in reticuloendothelial organs rather than those that facilitate drug excretion.…”

“…To this end, theranostics serve as a bridge between therapeutic and diagnostic tracking. Previous iterations of HIV-1 theranostics included spherical europium cobalt-ferrite (CFEu) 14 and bismuth sulfide nanorods (BSNRs) 15 . These particles, loaded with RPV 14 , 15 or dolutegravir (DTG; an INSTI) 16 , showed characteristics of enhanced particle uptake in macrophages.…”

“…Previous iterations of HIV-1 theranostics included spherical europium cobalt-ferrite (CFEu) 14 and bismuth sulfide nanorods (BSNRs) 15 . These particles, loaded with RPV 14 , 15 or dolutegravir (DTG; an INSTI) 16 , showed characteristics of enhanced particle uptake in macrophages. Real-time non-invasive tracking of nanoparticles biodistribution using fluorescence, magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT-CT) conferred by their metal cores or inserting radiolabel tags have allowed the prediction of drug biodistribution based on early bioimaging composite analyses 15 .…”

Pharmacotherapeutics of SARS-CoV-2 Infections

“…Dexamethasone is a potent anti-inflammatory corticosteroid and its nanoformuation is well known for the development of macrophages depot after intravenous and inhalation administration (Lammers et al 2020 ). The long-acting nanoformulation of anti HIV-1 drugs showed success as a macrophage-based drug carrier for anti-HIV-1 therapy compared to the free drug (Dash et al 2020 ; Kevadiya et al 2020 ; Kulkarni et al 2020 ; Mukadam et al 2020 ). Hence, this strategy might also work in COVID-19 treatment if alveolar macrophages targeting dexamethasone nanoparticles are designed ( Fig.…”