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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Research Article

Antitumor Effects of Docetaxel in Truncated Basic Fibroblast Growth Factor- Functionalized Liposomes Delivered by d-α-tocopheryl Polyethylene Glycol 2000 Succinate

Author(s): Jiaolin Wen, Zhoufeng Wang, Neng Qiu, Huili Liu, Xiaoming Shu, Zejiang Zhu, Peng Bai, Li Yang and Lijuan Chen*

Volume 26, Issue 34, 2020

Page: [4338 - 4348] Pages: 11

DOI: 10.2174/1381612826666200423093357

Price: $65

Abstract

Background: PEGylation of stealth liposomes elevates their stability and prolongs plasma half-life. Stealth liposomes modified with targeting ligands are expected to be ideal drug delivery carriers.

Objective: To encapsulate docetaxel in tbFGF (truncated basic fibroblast growth factor)-functionalized liposomes with mPEG2000-VE (d-α-tocopheryl polyethylene glycol succinate, TPGS2K) and measure their antitumor effects in vitro and in vivo.

Methods: TPGS2K and COOH-PEG2000-VE were synthesized, and tbFGF was conjugated to COOH-PEG2000-VE to prepare tbFGF-PEG2000-VE. Then, tbFGF-functionalized liposomes (DTX-tbFGF-LPs) were prepared by inserting tbFGF-PEG2000-VE into docetaxel liposomes comprising TPGS2K (DTX-PEG-LPs). The stabilities and drug release profiles of the formulation were evaluated. P-glycoprotein (P-gp) inhibition was measured by ATPase assay. MTT and cell uptake were measured with B16 cells. A B16 C57BL/6 mouse model was used to evaluate in vivo antitumor efficacy.

Results: Both DTX-PEG-LPs and DTX-tbFGF-LPs exhibited good stability and sustained drug release. MTT, flow cytometry, and fluorescence microscopy of B16 cells revealed higher antitumor activity and more efficient cell uptake for DTX-tbFGF-LPs compared with DTX-PEG-LPs and DTX-LPs. The P-gp ATPase assay showed that both PEG-LP and tbFGF-PEG-LP formulations inhibited P-gp pump activity in vitro. DTX-tbFGF-LPs had the highest antitumor efficacy and lowest toxicity in vivo.

Conclusion: Truncated basic fibroblast growth factor-functionalized liposomes with TPGS2K as drug delivery nanocarriers were effective chemotherapy agents targeting FGFR-overexpressing tumors.

Keywords: Truncated basic human fibroblast growth factor, d-α-tocopheryl polyethylene 2000 glycol succinate, docetaxel, liposome, antitumor, P-gp pump.

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