Tumor-targeting intravenous lipid emulsion of paclitaxel: Characteristics, stability, toxicity, and toxicokinetics

• Published in: Journal of pharmaceutical analysis Vol. 12; no. 6; pp. 901 - 912
• Main Authors: Ye, Jun, Li, Lin, Yin, Jiye, Wang, Hongliang, Li, Renjie, Yang, Yanfang, Guan, Yongbiao, Xia, Xuejun, Liu, Yuling
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.12.2022; Xi'an Jiaotong University, Journal of Pharmaceutical Analysis; Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China%National Beijing Center for Drug Safety Evaluation and Research,Beijing Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing,100850,China%Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China%State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China; Xi'an Jiaotong University; Elsevier
• Subjects: Acute toxicity; Antitumor activity; Body weight; Bone marrow; Breast cancer; Chemotherapy; Cholesterol; Clinical trials; Colloidal Stability; Drug dosages; Glycerol; Homogenization; Hypersensitivity; Intravenous administration; Laboratory animals; Lethal dose; Lipid emulsion; Lipids; Low density lipoprotein receptors; Myelosuppression; Nanodrug delivery systems; Nanoemulsions; Original; Paclitaxel; Particle size; Pharmaceuticals; Polyethylene glycol; Safety; Size distribution; Soybeans; Toxicokinetics; Tumors; Vitamin E; Beijing China; United States > US; China; Germany; Toxicokinetics; Colloidal Stability; Lipid emulsion; Nanodrug delivery systems; Paclitaxel
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2022.08.002

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel (PTX). However, no intravenous lipid emulsion of PTX has been approved for clinical treatment, and systemic safety profiles have not yet been reported. Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion (PTX Emul) and describe its characteristics, colloidal stability, and systemic safety profiles in terms of acute toxicity, long-term toxicity, and toxicokinetics. We also compare PTX Emul with conventional PTX injection. Results showed that PTX Emul exhibited an ideal average particle size (approximately 160 nm) with narrow size distribution and robust colloidal stability under different conditions. Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential. In addition, where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs, including the decreased AUC and increased plasma clearance and volume of distribution, PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose, moderate body weight change, decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose. A fundamental understanding of the systemic safety profiles, high tumor-targeting efficiency, and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer. [Display omitted] •The colloidal stability of PTX Emul was evaluated by static multiple light scattering.•The systemic safety profiles of PTX Emul were evaluated and compared with those of PTX injection.•The findings highlighted the therapeutic potential of PTX Emul as a future treatment for breast cancer.