title: Investigating the pharmacokinetics and biological distribution of silver-loaded polyphosphoester-based nanoparticles using (111) Ag as a radiotracer.
abstract: Purified (111) Ag was used as a radiotracer to investigate silver loading and release, pharmacokinetics, and biodistribution of polyphosphoester-based degradable shell crosslinked knedel-like (SCK) nanoparticles as a comparison to the previously reported small molecule, N-heterocyclic silver carbene complex analog (SCC1) for the delivery of therapeutic silver ions in mouse models. Biodistribution studies were conducted by aerosol administration of (111) Ag acetate, [(111) Ag]SCC1, and [(111) Ag]SCK doses directly into the lungs of C57BL/6 mice. Nebulization of the (111) Ag antimicrobials resulted in an average uptake of 1.07 ± 0.12% of the total aerosolized dose given per mouse. The average dose taken into the lungs of mice was estimated to be 2.6 ± 0.3% of the dose inhaled per mouse for [(111) Ag]SCC1 and twice as much dose was observed for the [(111) Ag]SCKs (5.0 ± 0.3% and 5.9 ± 0.8% for [(111) Ag]aSCK and [(111) Ag]zSCK, respectively) at 1 h post administration (p.a.). [(111) Ag]SCKs also exhibited higher dose retention in the lungs; 62-68% for [(111) Ag]SCKs and 43% for [(111) Ag]SCC1 of the initial 1 h dose were observed in the lungs at 24 h p.a.. This study demonstrates the utility of (111) Ag as a useful tool for monitoring the pharmacokinetics of silver-loaded antimicrobials in vivo.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Tolulope A
authors.initials: TA
authors.lastname: Aweda
authors.affiliation: Department of Chemistry, Texas A & M University, College Station, TX, 77843, USA.
authors.forename: Shiyi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Chiedza
authors.initials: C
authors.lastname: Mupanomunda
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Burkemper
authors.affiliation: Department of Chemistry, Texas A & M University, College Station, TX, 77843, USA.
authors.forename: Gyu Seong
authors.initials: GS
authors.lastname: Heo
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Nilantha
authors.initials: N
authors.lastname: Bandara
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Mai
authors.initials: M
authors.lastname: Lin
authors.affiliation: Research Reactor Center, University of Missouri, 230 Jesse Hall, Columbia, MO, 65211, USA.
authors.forename: Cathy S
authors.initials: CS
authors.lastname: Cutler
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, 407 Reynolds Medical Building, College Station, TX, 77843, USA.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Cannon
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH, 44325, USA.
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
authors.affiliation: Department of Chemistry, Texas A & M University, College Station, TX, 77843, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wooley
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Lapi
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D009943:Organophosphorus Compounds / Q000737:chemistry; D012834:Silver / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents; D009943:Organophosphorus Compounds; D012834:Silver
keywords: aerosols; autoradiography; biodistribution; nanoparticles; nose-only inhalation; pharmacokinetics; radiotracer; silver antimicrobials