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Int. J. Mol. Sci. 2014, 15(2), 2761-2772; doi:10.3390/ijms15022761
Article

Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model

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Received: 30 December 2013; in revised form: 10 February 2014 / Accepted: 11 February 2014 / Published: 18 February 2014
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Abstract: Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.
Keywords: multidrug-resistant breast cancer; vincristine; verapamil; PLGA nanoparticles; co-encapsulation multidrug-resistant breast cancer; vincristine; verapamil; PLGA nanoparticles; co-encapsulation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Chen, Y.; Zheng, X.-L.; Fang, D.-L.; Yang, Y.; Zhang, J.-K.; Li, H.-L.; Xu, B.; Lei, Y.; Ren, K.; Song, X.-R. Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model. Int. J. Mol. Sci. 2014, 15, 2761-2772.

AMA Style

Chen Y, Zheng X-L, Fang D-L, Yang Y, Zhang J-K, Li H-L, Xu B, Lei Y, Ren K, Song X-R. Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model. International Journal of Molecular Sciences. 2014; 15(2):2761-2772.

Chicago/Turabian Style

Chen, Yan; Zheng, Xue-Lian; Fang, Dai-Long; Yang, Yang; Zhang, Jin-Kun; Li, Hui-Li; Xu, Bei; Lei, Yi; Ren, Ke; Song, Xiang-Rong. 2014. "Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model." Int. J. Mol. Sci. 15, no. 2: 2761-2772.



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