International Journal of Nanomedicine (Jan 2023)

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

  • Lu J,
  • Lou Y,
  • Zhang Y,
  • Zhong R,
  • Zhang W,
  • Zhang X,
  • Wang H,
  • Chu T,
  • Han B,
  • Zhong H

Journal volume & issue
Vol. Volume 18
pp. 263 – 276

Abstract

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Jun Lu,1– 4,* Yuqing Lou,1,* Yanwei Zhang,1,* Runbo Zhong,1 Wei Zhang,1 Xueyan Zhang,1 Huimin Wang,1 Tianqing Chu,1 Baohui Han,1– 3 Hua Zhong1,3 1Department of Pulmonary Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Translational Medical Research Platform for Thoracic Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Bio-Bank, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohui Han; Hua Zhong, Department of Pulmonary Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China, Email [email protected]; [email protected]; [email protected]: 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.Graphical Abstract: Keywords: nanomedicine, polymeric micellar paclitaxel, NSCLC, toxicological profile

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