Size Exclusion of Radioactive Polymers (SERP) informs on the biodegradation of trimethyl chitosan and biodegradable polymer nanoparticles in vitro and in vivo

Preparation of drug delivery systems and nanomedicines necessitates the use of biocompatible excipients that are readily eliminated from the body. The systematic preclinical development of novel materials requires tools to evaluate their pharmacokinetics, biodistribution and excretion. Herein, we propose a technique called Size Exclusion of Radioactive Polymers (SERP) to trail the disposition of a radiolabeled polymer and its nanoparticles using chromatography in the presence of complex biological media such as blood, urine and feces. Trimethyl chitosan (TMC) is a polysaccharide of natural origin showing promise for controlled and targeted drug delivery applications. SERP was used to monitor degradation of radiolabeled TMC and its nanoparticles in vitro in the presence of strong acid, enzymes released by macrophages, as well as in vivo after administration to rats. Excretion of the radiolabeled TMC nanoparticles in urine and feces was monitored for 14 days after dosing to healthy rats, confirming that the polymer could be readily eliminated from the body. This work demonstrates the ability of SERP to understand the biological journey of biomaterials in vivo. Paving the way to understand the fate of polymers and nanoparticles in complex environments, the technique might facilitate the development of safer and better tolerated nanomedicines.