1. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy
- Author
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Xin Ming Liu, Tianyuzi Li, Tatiana K. Bronich, JoEllyn M McMillan, Michael D. Boska, Howard E. Gendelman, Benson J Edagwa, Gang Zhang, and Pavan Puligujja
- Subjects
Male ,theranostics ,Pharmaceutical Science ,02 engineering and technology ,Mice ,Drug Delivery Systems ,International Journal of Nanomedicine ,Drug Discovery ,Tissue Distribution ,Molecular Targeted Therapy ,Magnetite Nanoparticles ,Mononuclear Phagocyte System ,Original Research ,media_common ,Mice, Inbred BALB C ,0303 health sciences ,Alendronate ,Nanoart ,Dextrans ,General Medicine ,021001 nanoscience & nanotechnology ,Magnetic Resonance Imaging ,3. Good health ,Nanomedicine ,Anti-Retroviral Agents ,Drug delivery ,Systemic administration ,0210 nano-technology ,Drug ,Biodistribution ,magnetite ,Materials science ,media_common.quotation_subject ,Atazanavir Sulfate ,Biophysics ,Bioengineering ,Nanotechnology ,Biomaterials ,folic acid ,03 medical and health sciences ,Pharmacokinetics ,Animals ,030304 developmental biology ,Macrophages ,Organic Chemistry ,Reproducibility of Results ,Pharmacodynamics ,decorated nanoparticles ,Biomedical engineering - Abstract
Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery., Video abstract
- Published
- 2015