Investigating the pharmacokinetics and biological distribution of silver-loaded polyphosphoester-based nanoparticles using 111Ag as a radiotracer
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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. Copyright 2015 John Wiley & Sons, Ltd.
