期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 106, 期 10, 页码 3066-3075出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2017.05.027
关键词
paclitaxel; piperlongumine; nanoparticles; synergistic effect
资金
- National Natural Science Foundation of China [81473272, 81503148]
- Graduate Program of Scientific Research and Innovation in Jiangsu Province [KYLX15_0651]
The purpose of this study was to develop a nanocarrier system for codelivery of paclitaxel (PTX) and piperlongumine (PL) and investigate the therapeutic potential of improving efficacy and reducing toxicity. PTX and PL were formulated into poly lactic-co-glycolic acid and D-alpha-tocopheryl polyethylene glycol succinate via organic solvent evaporation method. The average diameter was 117.1 +/- 1.9 nm, and the zeta potential was -43.25 +/- 2.76 mV. PL facilitated the cellular uptake of PTX, and the increased cytotoxicity was similarly displayed. The formulation with the PTX/PL concentration ratio at 1: 200 showed the best antitumor activity, the IC50 of PTX were 5.10 +/- 0.08 nM in HepG2 cells, and 3.79 +/- 1.01 nM in Michigan Cancer Foundation-7 cells. Correspondingly, the combination index was 0.79 and 0.76. Furthermore, intracellular uptake of PTX toward HepG2 cells in coencapsulated nanoparticles was significantly more than free solution. In addition, the antitumor effect of PTX/PL-PTNPs in the HepG2 xenograft tumor model suggested that the nanoparticles showed a higher antitumor efficacy with reduced toxicity to other tissues compared with free PTX. In summary, the results indicated that PTX/PL-PTNPs processed well characteristics and enhanced its therapeutic efficacy; thus, this delivery system could be clinically effective for treatment of cancers. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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