摘要

In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (LsbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded LsbMDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded LsbMDDs formulations were examined and found to have a mean size of <200 nm, an encapsulation efficiency of >90%, and drug loading of >6% with stability at room temperature and at 4 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded LsbMDDs was slower than that from the generic product of DTX (Tynen®). A cell viability assay demonstrated that the LsbMDDs showed better cytotoxicity than Tynen® against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded LsbMDDs was observed to be better than that of Tynen® in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded LsbMDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen®, but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded LsbMDDs, and its maximal tolerable doses for single and repeated injections were 2–2.5-fold higher than those of Tynen®. In conclusion, the LsbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.
原文英語
頁(從 - 到)9-19
頁數11
期刊European Journal of Pharmaceutics and Biopharmaceutics
123
DOIs
出版狀態已發佈 - 二月 1 2018

指紋

docetaxel
Lecithins
Drug Delivery Systems
Therapeutics
Neoplasms
Pharmaceutical Preparations

Keywords

  • Docetaxel
  • DSPE-PEG2K
  • Lecithin
  • Lecithin-stabilized micelles
  • Ultrasonication

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

引用此文

@article{99d007a30e084d448a933d4e77fd2a9e,
title = "Development and characterization of docetaxel-loaded lecithin-stabilized micellar drug delivery system (LsbMDDs) for improving the therapeutic efficacy and reducing systemic toxicity",
abstract = "In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (LsbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded LsbMDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded LsbMDDs formulations were examined and found to have a mean size of <200 nm, an encapsulation efficiency of >90{\%}, and drug loading of >6{\%} with stability at room temperature and at 4 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded LsbMDDs was slower than that from the generic product of DTX (Tynen{\circledR}). A cell viability assay demonstrated that the LsbMDDs showed better cytotoxicity than Tynen{\circledR} against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded LsbMDDs was observed to be better than that of Tynen{\circledR} in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded LsbMDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen{\circledR}, but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded LsbMDDs, and its maximal tolerable doses for single and repeated injections were 2–2.5-fold higher than those of Tynen{\circledR}. In conclusion, the LsbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.",
keywords = "Docetaxel, DSPE-PEG2K, Lecithin, Lecithin-stabilized micelles, Ultrasonication, Docetaxel, DSPE-PEG2K, Lecithin, Lecithin-stabilized micelles, Ultrasonication",
author = "Su, {Chia Yu} and Liu, {Jun Jen} and Ho, {Yuan Soon} and Huang, {Yi You} and Chang, {Vincent Hung Shu} and Liu, {Der Zen} and Chen, {Ling Chun} and Ho, {Hsiu O.} and Sheu, {Ming Thau}",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.ejpb.2017.11.006",
language = "English",
volume = "123",
pages = "9--19",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",

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TY - JOUR

T1 - Development and characterization of docetaxel-loaded lecithin-stabilized micellar drug delivery system (LsbMDDs) for improving the therapeutic efficacy and reducing systemic toxicity

AU - Su, Chia Yu

AU - Liu, Jun Jen

AU - Ho, Yuan Soon

AU - Huang, Yi You

AU - Chang, Vincent Hung Shu

AU - Liu, Der Zen

AU - Chen, Ling Chun

AU - Ho, Hsiu O.

AU - Sheu, Ming Thau

PY - 2018/2/1

Y1 - 2018/2/1

N2 - In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (LsbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded LsbMDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded LsbMDDs formulations were examined and found to have a mean size of <200 nm, an encapsulation efficiency of >90%, and drug loading of >6% with stability at room temperature and at 4 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded LsbMDDs was slower than that from the generic product of DTX (Tynen®). A cell viability assay demonstrated that the LsbMDDs showed better cytotoxicity than Tynen® against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded LsbMDDs was observed to be better than that of Tynen® in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded LsbMDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen®, but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded LsbMDDs, and its maximal tolerable doses for single and repeated injections were 2–2.5-fold higher than those of Tynen®. In conclusion, the LsbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.

AB - In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (LsbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded LsbMDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded LsbMDDs formulations were examined and found to have a mean size of <200 nm, an encapsulation efficiency of >90%, and drug loading of >6% with stability at room temperature and at 4 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded LsbMDDs was slower than that from the generic product of DTX (Tynen®). A cell viability assay demonstrated that the LsbMDDs showed better cytotoxicity than Tynen® against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded LsbMDDs was observed to be better than that of Tynen® in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded LsbMDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen®, but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded LsbMDDs, and its maximal tolerable doses for single and repeated injections were 2–2.5-fold higher than those of Tynen®. In conclusion, the LsbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.

KW - Docetaxel

KW - DSPE-PEG2K

KW - Lecithin

KW - Lecithin-stabilized micelles

KW - Ultrasonication

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KW - DSPE-PEG2K

KW - Lecithin

KW - Lecithin-stabilized micelles

KW - Ultrasonication

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M3 - Article

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JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

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