Therapeutic efficacy of lipid emulsions of docetaxel-linoleic acid conjugate in breast cancer.

Abstract

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.

• Authors: Tao Zhang, Meng Li, Ruyi Yang, Dong Zhang, Jibin Guan, Jiang Yu, Bin Yang, Huicong Zhang, Shenwu Zhang, Dan Liu, Yongjun Wang
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 546 Issue 1-2 Pg. 61-69 (Jul 30 2018) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 29763687 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Emulsions
• Taxoids
• Docetaxel
• Linoleic Acid

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Apoptosis (drug effects)
• Biological Availability
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Docetaxel
• Drug Carriers (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Emulsions
• Female
• Linoleic Acid (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Male
• Mice
• Mice, Inbred BALB C
• Rats, Sprague-Dawley
• Taxoids (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Treatment Outcome
• Tumor Burden (drug effects)