Paclitaxel Has a Reduced Toxicity Profile in Healthy Rats After Polymeric Micellar Nanoparticle Delivery

Int J Nanomedicine. 2023 Jan 13:18:263-276. doi: 10.2147/IJN.S372961. eCollection 2023.

Abstract

Background: Nanocarrier platforms have been indicated to have great potential in clinical practice to treat non-small cell lung cancer (NSCLC). Our previous Phase III clinical study revealed that polymeric micellar paclitaxel (Pm-Pac) is safe and efficacious in advanced NSCLC patients. However, the histopathological-toxicological profile of Pm-Pac in mammals remains unclear.

Methods: We examined the Pm-Pac-induced antitumour effect in both A549/H226 cells and A549/H226-derived xenograft tumour models.. And then, we evaluated the short-term and long-term toxicity induced by Pm-Pac in healthy Sprague‒Dawley (SD) rats. The changes in body weight, survival, peripheral neuropathy, haematology, and histopathology were studied in SD rats administered Pm-Pac at different dosages.

Results: In the A549-derived xenograft tumour model, better therapeutic efficacy was observed in the Pm-Pac group than in the solvent-based paclitaxel (Sb-Pac) group when an equal dosage of paclitaxel was administered. Toxicity assessments in healthy SD rats indicated that Pm-Pac caused toxicity at an approximately 2- to 3-fold greater dose than Sb-Pac when examining animal body weight, survival, peripheral neuropathy, haematology, and histopathology. Interestingly, based on histopathological examinations, we found that Pm-Pac could significantly decrease the incidences of paclitaxel-induced brain and liver injury but could potentially increase the prevalence of paclitaxel-induced male genital system toxicity.

Conclusion: This study introduces the toxicological profile of the engineered nanoparticle Pm-Pac and provides a novel perspective on the Pm-Pac-induced histopathological-toxicological profile in a rat model.

Keywords: NSCLC; nanomedicine; polymeric micellar paclitaxel; toxicological profile.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic*
  • Body Weight
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Disease Models, Animal
  • Humans
  • Lung Neoplasms* / drug therapy
  • Male
  • Mammals
  • Micelles
  • Nanoparticles* / toxicity
  • Paclitaxel / pharmacology
  • Peripheral Nervous System Diseases* / drug therapy
  • Polymers
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Paclitaxel
  • Antineoplastic Agents, Phytogenic
  • Micelles
  • Polymers

Grants and funding

This work was supported by the foundation of National Natural Science Foundation of China grants (Project No. 82272913); Shanghai Chest Hospital (Project No. 2019YNJCM11 & YJXT20190102); the Shanghai Leading Talents Program (2013), the program of Shanghai Jiao Tong University (Project No. YG2021QN121); the foundation of Chinese society of clinical oncology (Project No. Y-2019AZZD-0355 & Y-QL2019-0125); National Multi-disciplinary Treatment Project for Major Disease (Project No. 2020NMDTP).