PEG2000-PLA-based nanoscale polymeric micelles reduce paclitaxel-related toxicity in beagle dogs
Nanoplatform-based drug delivery plays an important role in clinical practice. Polymeric micellar (Pm) nanocarriers have been demonstrated to reduce the toxicity of paclitaxel in rats and non-small cell lung cancer (NSCLC) patients. However, the underlying toxicological profile needs to be further i...
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| Published in | Journal of controlled release Vol. 362; pp. 197 - 209 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Elsevier B.V
01.10.2023
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| Abstract | Nanoplatform-based drug delivery plays an important role in clinical practice. Polymeric micellar (Pm) nanocarriers have been demonstrated to reduce the toxicity of paclitaxel in rats and non-small cell lung cancer (NSCLC) patients. However, the underlying toxicological profile needs to be further illustrated. Here, we used beagles as study subjects and sought to further observe the toxicological profile of polymeric micellar paclitaxel (Pm-Pac) via acute toxicity tests and short-term and long-term toxicity tests. The results from the acute toxicity test indicated that the lethal dose of Pm-Pac in beagles was 20–30 mg/kg, and the acute toxicity-targeted organs were the digestive system and immuno-haematopoietic system. The short-term toxicity test suggested that paclitaxel-induced toxicity (peripheral neuropathy toxicity, haemopoietic toxicity, heart system toxicity, and so on) in beagles can be reduced when paclitaxel is delivered via the Pm delivery system. The long-term toxicity test suggested that Pm-Pac can reduce haemopoietic toxicity in beagles. Collectively, this study provides novel insight into the toxicological profile of Pm-Pac in healthy beagles and provides a potential basis for promising clinical combination strategies in the future.
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| AbstractList | Nanoplatform-based drug delivery plays an important role in clinical practice. Polymeric micellar (Pm) nanocarriers have been demonstrated to reduce the toxicity of paclitaxel in rats and non-small cell lung cancer (NSCLC) patients. However, the underlying toxicological profile needs to be further illustrated. Here, we used beagles as study subjects and sought to further observe the toxicological profile of polymeric micellar paclitaxel (Pm-Pac) via acute toxicity tests and short-term and long-term toxicity tests. The results from the acute toxicity test indicated that the lethal dose of Pm-Pac in beagles was 20-30 mg/kg, and the acute toxicity-targeted organs were the digestive system and immuno-haematopoietic system. The short-term toxicity test suggested that paclitaxel-induced toxicity (peripheral neuropathy toxicity, haemopoietic toxicity, heart system toxicity, and so on) in beagles can be reduced when paclitaxel is delivered via the Pm delivery system. The long-term toxicity test suggested that Pm-Pac can reduce haemopoietic toxicity in beagles. Collectively, this study provides novel insight into the toxicological profile of Pm-Pac in healthy beagles and provides a potential basis for promising clinical combination strategies in the future. Nanoplatform-based drug delivery plays an important role in clinical practice. Polymeric micellar (Pm) nanocarriers have been demonstrated to reduce the toxicity of paclitaxel in rats and non-small cell lung cancer (NSCLC) patients. However, the underlying toxicological profile needs to be further illustrated. Here, we used beagles as study subjects and sought to further observe the toxicological profile of polymeric micellar paclitaxel (Pm-Pac) via acute toxicity tests and short-term and long-term toxicity tests. The results from the acute toxicity test indicated that the lethal dose of Pm-Pac in beagles was 20-30 mg/kg, and the acute toxicity-targeted organs were the digestive system and immuno-haematopoietic system. The short-term toxicity test suggested that paclitaxel-induced toxicity (peripheral neuropathy toxicity, haemopoietic toxicity, heart system toxicity, and so on) in beagles can be reduced when paclitaxel is delivered via the Pm delivery system. The long-term toxicity test suggested that Pm-Pac can reduce haemopoietic toxicity in beagles. Collectively, this study provides novel insight into the toxicological profile of Pm-Pac in healthy beagles and provides a potential basis for promising clinical combination strategies in the future.Nanoplatform-based drug delivery plays an important role in clinical practice. Polymeric micellar (Pm) nanocarriers have been demonstrated to reduce the toxicity of paclitaxel in rats and non-small cell lung cancer (NSCLC) patients. However, the underlying toxicological profile needs to be further illustrated. Here, we used beagles as study subjects and sought to further observe the toxicological profile of polymeric micellar paclitaxel (Pm-Pac) via acute toxicity tests and short-term and long-term toxicity tests. The results from the acute toxicity test indicated that the lethal dose of Pm-Pac in beagles was 20-30 mg/kg, and the acute toxicity-targeted organs were the digestive system and immuno-haematopoietic system. The short-term toxicity test suggested that paclitaxel-induced toxicity (peripheral neuropathy toxicity, haemopoietic toxicity, heart system toxicity, and so on) in beagles can be reduced when paclitaxel is delivered via the Pm delivery system. The long-term toxicity test suggested that Pm-Pac can reduce haemopoietic toxicity in beagles. Collectively, this study provides novel insight into the toxicological profile of Pm-Pac in healthy beagles and provides a potential basis for promising clinical combination strategies in the future. Nanoplatform-based drug delivery plays an important role in clinical practice. Polymeric micellar (Pm) nanocarriers have been demonstrated to reduce the toxicity of paclitaxel in rats and non-small cell lung cancer (NSCLC) patients. However, the underlying toxicological profile needs to be further illustrated. Here, we used beagles as study subjects and sought to further observe the toxicological profile of polymeric micellar paclitaxel (Pm-Pac) via acute toxicity tests and short-term and long-term toxicity tests. The results from the acute toxicity test indicated that the lethal dose of Pm-Pac in beagles was 20–30 mg/kg, and the acute toxicity-targeted organs were the digestive system and immuno-haematopoietic system. The short-term toxicity test suggested that paclitaxel-induced toxicity (peripheral neuropathy toxicity, haemopoietic toxicity, heart system toxicity, and so on) in beagles can be reduced when paclitaxel is delivered via the Pm delivery system. The long-term toxicity test suggested that Pm-Pac can reduce haemopoietic toxicity in beagles. Collectively, this study provides novel insight into the toxicological profile of Pm-Pac in healthy beagles and provides a potential basis for promising clinical combination strategies in the future. [Display omitted] |
| Author | Wang, Shuyuan Han, Baohui Zhou, Chao Zhang, Yanwei Zhong, Hua Zou, Benkun Lou, Yuqing Hu, Minjuan Qian, Fangfei Chu, Tianqing Zhang, Bo Lu, Jun Liu, Hongyu Zhou, Jingsong Han, Bo |
| Author_xml | – sequence: 1 givenname: Jun surname: Lu fullname: Lu, Jun organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 2 givenname: Bo surname: Han fullname: Han, Bo organization: Department of General Surgery, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 3 givenname: Bo surname: Zhang fullname: Zhang, Bo organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 4 givenname: Benkun surname: Zou fullname: Zou, Benkun organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 5 givenname: Minjuan surname: Hu fullname: Hu, Minjuan organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 6 givenname: Hongyu surname: Liu fullname: Liu, Hongyu organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 7 givenname: Chao surname: Zhou fullname: Zhou, Chao organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 8 givenname: Fangfei surname: Qian fullname: Qian, Fangfei organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 9 givenname: Shuyuan surname: Wang fullname: Wang, Shuyuan organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 10 givenname: Yanwei surname: Zhang fullname: Zhang, Yanwei organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 11 givenname: Yuqing surname: Lou fullname: Lou, Yuqing organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 12 givenname: Tianqing surname: Chu fullname: Chu, Tianqing organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 13 givenname: Jingsong surname: Zhou fullname: Zhou, Jingsong email: zjs@yizhongpharma.com organization: Shanghai Yizhong Biotechnical Co., Ltd., Shanghai, China – sequence: 14 givenname: Baohui surname: Han fullname: Han, Baohui email: xkyyhan@gmail.com organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China – sequence: 15 givenname: Hua surname: Zhong fullname: Zhong, Hua email: eddiedong8@hotmail.com organization: Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China |
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| Keywords | LYMPH MCV PT ALP Sb-Pac ALT hr AUC GLU RBC MPV PFS Pm HGB Ctrl NEUT Nanocarrier MCHC T.P HCT Polymeric micellar FDA Toxicity BASO T.CHO MONO ORR PDI CREA ANOVA Paclitaxel WBC PLT BUN Pm-Pac HPLC Cmax AST NSCLC RDW EOS CK γ-GT ECG CL MCH TG ALB Beagles model PK TEM HE T.BIL RETIC |
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| Title | PEG2000-PLA-based nanoscale polymeric micelles reduce paclitaxel-related toxicity in beagle dogs |
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