Acute Toxicity, Biodistribution, and Pharmacokinetics Studies of Pegylated Platinum Nanoparticles in Mouse Model

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.

Platinum nanoplatforms: classic catalysts claiming a prominent role in cancer therapy

“…In contrast, the administration of higher doses at 50 mg kg À1 indicated a remarkable toxicity. 40 Finally, histopathological analyses at tissue level revealed no major reactive changes (such as vascular, degenerative, inflammatory, or hyperplastic changes) in the control group and in the group dosed with Pt NPs at 10 mg kg À1 . However, mice treated with 50 mg kg À1 PVP-Pt NPs exhibited significant nephrotoxicity and inflammation in the brain.…”

“…However, mice treated with 50 mg kg À1 PVP-Pt NPs exhibited significant nephrotoxicity and inflammation in the brain. 40 The PKs studies in the same work 40 indicated that after injection of 10 mg kg À1 dose, the time required to reach maximum levels of Pt NPs in blood plasma was 1 h and time for clearance at 50% in the plasma reached to 135 hours. The biodistribution studies showed the deposition of excess of Pt NPs in major organs such as liver, heart, lungs or kidney.…”

“…69 In vivo studies reporting Pt NPs behaviour in mice model have been so far scarcely reported. 40,65 Mukherjee et al 40 have recently carried out a comprehensive investigation exploring the toxicity, biodistribution, clearance and PKs of Pt NPs in female C57BL6/J mice models. They synthetized polyvinylpyrrolydone (PVP) coated Pt NPs with size in the range of 2-10 nm and they injected intraperitoneal doses of Pt NPs of 10 and 50 mg kg À1 .…”

“…However, despite the advances in this field, no exhaustive analysis of the role of Pt nanoparticles in biomedical applications has been published beyond that of Pedone et al 17 six years ago, although later works have paid specific attention on important aspects. Thus, Mukherjee et al 40 discussed biodistribution and toxicity features of PEGylated Pt NPs in murine models. Other recent publications have touched marginal aspects on this topic mainly focusing on toxicology 4 or on the interaction with a specific analyte ( e.g.…”

Platinum Nanoparticles in Biomedicine: Preparation, Anti-Cancer Activity, and Drug Delivery Vehicles

“…These features have the potential to circumvent some drawbacks of conventional pharmaceuticals, such as unfavorable side effects, imperfect selectivity, and undesirable pharmacokinetics. Some current efforts were done to synthesize more biocompatible platinum nanoparticles which are hemocompatible ( Mukherjee et al, 2021 ).…”