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Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo

Authors Wang W, Xi M, Duan X, Wang Y, Kong F

Received 4 January 2015

Accepted for publication 18 February 2015

Published 22 May 2015 Volume 2015:10(1) Pages 3737—3750

DOI https://doi.org/10.2147/IJN.S80297

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Lei Yang

Wei Wang,1,* Mei Xi,2,* Xuezhong Duan,1 Yong Wang,3 Fansheng Kong4

1Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji’nan Command, People’s Liberation Army, 2Emergency Department, The Fourth People’s Hospital of Ji’nan, Medical School, Tai Shan Medical College, 3Department of Rehabilitation and Physiotherapy, General Hospital of Ji’nan Command, People’s Liberation Army, 4Department of Hematology, General Hospital of Ji’nan Command, People’s Liberation Army, Ji’nan, People’s Republic of China

*These authors contributed equally to this work

Purpose: Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance. The aim of the study reported here was to develop multifunctional, dual-ligand, modified, self-assembled nanoparticles (NPs) for the combination delivery of baicalein (BCL) and paclitaxel (PTX) prodrugs.
Methods: Prodrug of PTX and prodrug of BCL, containing dual-targeted ligands of folate (FA) and hyaluronic acid (HA), were synthesized. Multifunctional self-assembled NPs for combination delivery of PTX prodrug and BCL prodrug (PTX-BCL) were prepared and the synergistic antitumor effect was evaluated in vitro and in vivo. The in vitro transfection efficiency of the novel modified vectors was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/PTX cells. The in vivo antitumor efficiency and systemic toxicity of different formulations were further investigated in mice bearing A549/PTX drug-resistant human lung cancer xenografts.
Results: The size of the PTX-BCL NPs was approximately 90 nm, with a positive zeta potential of +3.3. The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations.
Conclusion: The prepared PTX-BCL NP drug-delivery system was proven efficient by its targeting of drug-resistant human lung cancer cells and delivering of BCL and PTX prodrugs. Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine.

Keywords: combination chemotherapy, prodrug-based nano-drug delivery system, multidrug resistance, self-assembled nanoparticles

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