TY - JOUR
T1 - Therapeutic efficacy of lipid emulsions of docetaxel-linoleic acid conjugate in breast cancer
AU - Zhang, Tao
AU - Li, Meng
AU - Yang, Ruyi
AU - Zhang, Dong
AU - Guan, Jibin
AU - Yu, Jiang
AU - Yang, Bin
AU - Zhang, Huicong
AU - Zhang, Shenwu
AU - Liu, Dan
AU - Wang, Yongjun
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/7/30
Y1 - 2018/7/30
N2 - Docetaxel (DTX) solution is among the most widely-used parenteral formulations used in advanced breast cancer therapy. However, severe side effects have been observed due to the use of ethanol and polysorbate 80. Herein, a novel DTX-based prodrug, docetaxel-linoleic acid conjugate (DTX-LA) was successfully synthesized. The high lipid solubility of DTX and DTX-LA resulted in a tendency for them to become entrapped in the oil core of the emulsions. As anticipated, nano-sized, sterically stabilized oil-in-water lipid emulsions (LMs) of DTX-LA LMs and DTX LMs were successfully constructed. Unlike DTX solution, LMs exhibited high colloidal stability and sustained-release behavior, having a narrow size distribution that was ∼220 nm in diameter. Compared with DTX LMs, DTX-LA LMs had a greater drug-loading capacity. Although the cytotoxicity of DTX-LA LMs was reduced in comparison with DTX solution, the pharmacokinetic study demonstrated increased bioavailability (p < 0.001) and half-life (p < 0.01). Finally, DTX-LA LMs displayed significant antitumor efficacy with reduced side effects in a 4T1 breast cancer xenograft model. Thus, the novel lipid emulsion-based docetaxel prodrug delivery system may be a promising strategy for improving intravenous administration for breast cancer treatment.
AB - Docetaxel (DTX) solution is among the most widely-used parenteral formulations used in advanced breast cancer therapy. However, severe side effects have been observed due to the use of ethanol and polysorbate 80. Herein, a novel DTX-based prodrug, docetaxel-linoleic acid conjugate (DTX-LA) was successfully synthesized. The high lipid solubility of DTX and DTX-LA resulted in a tendency for them to become entrapped in the oil core of the emulsions. As anticipated, nano-sized, sterically stabilized oil-in-water lipid emulsions (LMs) of DTX-LA LMs and DTX LMs were successfully constructed. Unlike DTX solution, LMs exhibited high colloidal stability and sustained-release behavior, having a narrow size distribution that was ∼220 nm in diameter. Compared with DTX LMs, DTX-LA LMs had a greater drug-loading capacity. Although the cytotoxicity of DTX-LA LMs was reduced in comparison with DTX solution, the pharmacokinetic study demonstrated increased bioavailability (p < 0.001) and half-life (p < 0.01). Finally, DTX-LA LMs displayed significant antitumor efficacy with reduced side effects in a 4T1 breast cancer xenograft model. Thus, the novel lipid emulsion-based docetaxel prodrug delivery system may be a promising strategy for improving intravenous administration for breast cancer treatment.
KW - Breast cancer therapy
KW - Docetaxel (DTX)
KW - Docetaxel-linoleic acid conjugate (DTX-LA)
KW - Lipid emulsions
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U2 - 10.1016/j.ijpharm.2018.05.032
DO - 10.1016/j.ijpharm.2018.05.032
M3 - Article
C2 - 29763687
AN - SCOPUS:85047273991
SN - 0378-5173
VL - 546
SP - 61
EP - 69
JO - International journal of pharmaceutics
JF - International journal of pharmaceutics
IS - 1-2
ER -
