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Co-delivery of doxorubicin and imatinib by pH sensitive cleavable PEGylated nanoliposomes with folate-mediated targeting to overcome multidrug resistance.

Abstract
Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment. Moreover, the IM in combination therapy could overcome chemoresistance associated with DOX effectively by inhibiting ABC transporter function and improving chemotherapy sensitivity. The designed liposomes co-loaded with DOX and IM significantly enhanced anti-tumor effects both in vitro and in vivo. These findings suggest that FPL-DOX/IM provides a novel strategy to improve chemotherapeutic efficacy against MDR tumors.
AuthorsYan Chen, Yao Cheng, Pengxuan Zhao, Shasha Zhang, Minsi Li, Chuanchuan He, Xiaojuan Zhang, Tan Yang, Ruicong Yan, Peng Ye, Xiang Ma, Guangya Xiang
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 542 Issue 1-2 Pg. 266-279 (May 05 2018) ISSN: 1873-3476 [Electronic] Netherlands
PMID29551747 (Publication Type: Journal Article)
CopyrightCopyright © 2018. Published by Elsevier B.V.
Chemical References
  • Folate Receptors, GPI-Anchored
  • Liposomes
  • Vitamin E
  • Doxorubicin
  • Imatinib Mesylate
  • Folic Acid
  • tocophersolan
Topics
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, chemistry, pharmacokinetics)
  • Apoptosis (drug effects)
  • Cell Survival (drug effects)
  • Doxorubicin (administration & dosage, chemistry, pharmacokinetics)
  • Drug Liberation
  • Drug Resistance, Neoplasm
  • Drug Stability
  • Female
  • Folate Receptors, GPI-Anchored (metabolism)
  • Folic Acid (administration & dosage, chemistry, pharmacokinetics)
  • Humans
  • Hydrogen-Ion Concentration
  • Imatinib Mesylate (administration & dosage, chemistry, pharmacokinetics)
  • Liposomes
  • MCF-7 Cells
  • Mice, Inbred BALB C
  • Mice, Nude
  • Vitamin E (administration & dosage, chemistry, pharmacokinetics)

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