title: Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.
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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Tianyuzi
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA ; Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Puligujja
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: JoEllyn M
authors.initials: JM
authors.lastname: McMillan
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Bronich
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Benson
authors.initials: B
authors.lastname: Edagwa
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA ; Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
mesh_terms: D019386:Alendronate / Q000737:chemistry; D000818:Animals; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate / Q000493:pharmacokinetics; D003911:Dextrans; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D008264:Macrophages / Q000187:drug effects; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy / Q000379:methods; D012157:Mononuclear Phagocyte System / Q000187:drug effects; D050997:Nanomedicine / Q000379:methods; D015203:Reproducibility of Results; D014018:Tissue Distribution
chemical_list: D044966:Anti-Retroviral Agents; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D000069446:Atazanavir Sulfate; D005492:Folic Acid; D019386:Alendronate
keywords: decorated nanoparticles; folic acid; magnetic resonance imaging; magnetite; theranostics