Investigating the pharmacokinetics and biological distribution of silver-loaded polyphosphoester-based nanoparticles using 111Ag as a radiotracer

Tolulope A. Aweda, Shiyi Zhang, Chiedza Mupanomunda, Jennifer Burkemper, Gyu Seong Heo, Nilantha Bandara, Mai Lin, Cathy S. Cutler, Carolyn L. Cannon, Wiley J. Youngs, Karen L. Wooley, Suzanne E. Lapi

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Purified 111Ag 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 111Ag acetate, [111Ag]SCC1, and [111Ag]SCK doses directly into the lungs of C57BL/6 mice. Nebulization of the 111Ag 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 [111Ag]SCC1 and twice as much dose was observed for the [111Ag]SCKs (5.0 ± 0.3% and 5.9 ± 0.8% for [111Ag]aSCK and [111Ag]zSCK, respectively) at 1 h post administration (p.a.). [111Ag]SCKs also exhibited higher dose retention in the lungs; 62-68% for [111Ag]SCKs and 43% for [111Ag]SCC1 of the initial 1 h dose were observed in the lungs at 24 h p.a. This study demonstrates the utility of 111Ag as a useful tool for monitoring the pharmacokinetics of silver-loaded antimicrobials in vivo. Purified 111Ag 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 an alternative to the small molecule, N-heterocyclic silver carbene complex (SCC1) for aerosol delivery of therapeutic silver in mouse models. Twice as much dose was observed in the lungs for [111Ag]SCKs (5.0 ± 0.3% and 5.9 ± 0.8% for [111Ag]aSCK and [111Ag]zSCK, respectively) compared with 2.6 ± 0.3% for [111Ag]SCC1 at 1 h post inhalation.

Original languageEnglish
Pages (from-to)234-241
Number of pages8
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume58
Issue number6
DOIs
StatePublished - May 30 2015

Keywords

  • aerosols
  • autoradiography
  • biodistribution
  • nanoparticles
  • nose-only inhalation
  • pharmacokinetics
  • radiotracer
  • silver antimicrobials

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