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Docetaxel-Loaded Lecithoid Nanoparticles with Enhanced Lung Targeting Efficiency and Reduced Systemic Toxicity: Developed by Solid Dispersion and Effervescent Techniques.

Authors
  • Zhang, Li1
  • Liu, Zhong-Hong1
  • Cheng, Xun-Guan1
  • Xia, Zhu2
  • Liu, Yu3
  • Yu, Yu1
  • 1 Research Laboratory of Medicinal Chemistry and Biomaterials, Chongqing Pharmaceutical Engineering Research Center, School of Pharmacy, Chongqing Medical University.
  • 2 Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University.
  • 3 Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University.
Type
Published Article
Journal
Chemical and Pharmaceutical Bulletin
Publisher
Pharmaceutical Society of Japan
Publication Date
Oct 01, 2017
Volume
65
Issue
10
Pages
959–966
Identifiers
DOI: 10.1248/cpb.c17-00515
PMID: 28781335
Source
Medline
Keywords
License
Unknown

Abstract

The application of chemotherapeutics with chemical drugs is always challenged by their high toxicities throughout the body in clinical trials. Here, we reported a smart formulation of docetaxel developed by solid dispersion and effervescent techniques for efficient and safe delivery of chemical drug to lung tissue. To achieve a high delivery to lung with reduced systemic toxicity, docetaxel was loaded into a kind of lecithoid nanoparticles (DTX-LN) which were prepared by a solid dispersion and effervescent method. After intravenous administration of DTX-LN to rabbit, the docetaxel level in lung was approximately 37-fold higher than that of docetaxel injection (DTX-INJ, a commercial injection preparation of DTX/polysorbate 80 micelles) group at 0.5 h and showed the highest tissue distribution among all the organs. Besides, the targeting parameter Re value of total increased amount of DTX in lung (AUC0-t) ratio (DTX-LN to DTX-INJ) is about 16.69, indicating a significantly enhanced lung targeting ability of DTX-LN. In subacute toxicity study, DTX-LN displayed a reduced hematotoxicity, especially for the negative impacts on white blood cells, lymphocyte and granulocyte when compared with DTX-INJ during both weekly and 3-weekly schedules administration. In addition, histopathological analysis demonstrated that DTX-LN showed less tissue damages on rabbit heart and kidney compared to DTX-INJ. Hence, this work would provide an insight for improving lung delivery efficacy of drugs with reduced systemic toxicity.

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