Acute Toxicity, Biodistribution, and Pharmacokinetics Studies of Pegylated Platinum Nanoparticles in Mouse Model
Sudip Mukherjee, Vishnu Sravan Bollu, Arpita Roy, Susheel Kumar Nethi, Madhusudana Kuncha, Jerald Mahesh Kumar, Ramakrishna Sistla, Chitta Ranjan Patra
Abstract
Pegylated colloidal platinum nanoparticles (PEG‐PtNPs) are widely used as a potential agent for diagnosis and therapy of various diseases including cancer. Prior to any preclinical applications, detailed investigations of toxicity, biodistribution, clearance, and pharmacokinetics (PKs) of new nanomaterials are essential. Extensive toxicological studies of PEG‐PtNPs are not reported in a systematic manner elsewhere. Herein, acute toxicity of PEG‐PtNPs is thoroughly investigated in mouse model. Prior to study in mice, a hemolytic analysis is performed with PtNPs that displays biocompatible nature. Administration of a single intraperitoneal dose of PEG‐PtNPs (10 and 50 mg kg −1 body weight) in mice does not induce any gross pathological changes. The data obtained from hematology, serum biochemistry, and histopathological analysis indicate no significant changes except for moderate nephrotoxicity at the higher dose. In addition, a PK analysis displays a maximum retention time and elimination half‐life at 10 mg kg −1 b.w. dose. Biodistribution studies demonstrate maximum accumulation of platinum in spleen tissue and tail of mice. Finally, detection of platinum in feces and urine confirms their excretion through a hepatobiliary system. Altogether, this study indicates that 10 mg kg −1 b.w. therapeutic dose of PEG‐PtNPs is safe for their potential future application in cancer theranostics.