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Acetic acid transporter-mediated, oral, multifunctional polymer liposomes for oral delivery of docetaxel.

Authors
  • Guo, XinHong1
  • Zhang, JunYa2
  • Cai, QingQing2
  • Fan, ShuTing2
  • Xu, QingQing2
  • Zang, JieYing2
  • Yang, HuiTing2
  • Yu, WenJuan2
  • Li, Zhi3
  • Zhang, ZhenZhong4
  • 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; Henan Key Laboratory of Targeted Therapy and Diagnosis of Tumor and Major Diseases, Henan Province, Zhengzhou, 450001, China. , (China)
  • 2 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China. , (China)
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; Henan Key Laboratory of Targeted Therapy and Diagnosis of Tumor and Major Diseases, Henan Province, Zhengzhou, 450001, China. Electronic address: [email protected] , (China)
  • 4 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; Henan Key Laboratory of Targeted Therapy and Diagnosis of Tumor and Major Diseases, Henan Province, Zhengzhou, 450001, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Colloids and surfaces. B, Biointerfaces
Publication Date
Feb 01, 2021
Volume
198
Pages
111499–111499
Identifiers
DOI: 10.1016/j.colsurfb.2020.111499
PMID: 33317899
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Nanoparticle-structuring aimed at the acetic acid (A) transporter on intestinal epithelial cells and tumor cells is a new potential strategy to enhance oral bioavailability and anti-tumor efficacy. In this study, chitosan (CS) was modified with hydrophilic A and hydrophobic lipoic acid (L), to produce ACSL. A novel ACSL-modified multifunctional liposomes (Lip) loaded with docetaxel (DTX; DTX-ACSL-Lip) was then prepared and characterized. DTX-ACSL-Lip recorded higher pH sensitivity and slower release than DTX-Lip and showed dithiothreitol (DTT) response release. DTX-ACSL-Lip uptake by Caco-2 cells was also significantly enhanced mainly viaA transporters compared with DTX-Lip. ACSL modification of DTX-Lip also improved oral bioavailability by 10.70-folds, with a 3.45-fold increase in Cmax and a 1.19-fold prolongation in retention time of DTX in the blood. Moreover, the grafting degree of A significantly affected cell uptake and oral bioavailability. They also showed a significant (1.33-fold) increase in drug intratumoral distribution, as well as an increase in tumor growth inhibition rate from 54.34% to 87.51% without weight loss, compared with DTX-Lip. Therefore, modification of DTX-Lip with ACSL can significantly enhance the oral bioavailability and anti-tumor efficacy of DTX without obvious toxicity, confirming the potential of the dual strategy of targeting A transporter and controlled drug release in tumor cells in oral therapy of tumor. Copyright © 2020 Elsevier B.V. All rights reserved.

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