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

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.