4.5 Article

In vivo study of poly (ethylene glycol)-poly (caprolactone)-modified folic acid nanocarriers as a pH responsive system for tumor-targeted co-delivery of tamoxifen and quercetin

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DOI: 10.1016/j.jddst.2019.101283

Keywords

In vivo study; Synergistic effect; Quercetin; Folate receptor; Drug delivery; Tamoxifen

Funding

  1. Faculty of Pharmacy, Zanjan University of Medical Sciences [A-12-430-28]

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In this project FA-L-PEG-PCL (FA: Folic acid, L: Lysine, PEG: Polyethylene glycol, PCL: Polycaprolactone) polymeric nanocarriers (NCs) were synthesized. In aqueous medium, this polymeric NCs could be self-assembled to form Round-shaped folate-functionalized micelles for delivery of Tamoxifen (TMX) and Quercetin (QUER) to cancerous cells. For determining the structure of this copolymer, fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and zeta sizer were used. The cytotoxicity of NCs was determined by hemolysis assay and this test displayed that the cytotoxicity of NCs is lower than 3%. To determine anticancer activity of synthesized drug loaded nanocarriers in vitro cell cytotoxicity analysis were performed on 4T1 cell line and in vivo treatment of tumors. Beside, histopathological study was performed to investigate the effect of drug loaded NCs on mice tissues. In vitro MTT experiment showed that QUER has significant synergistic effect for decreasing viability of the cancerous cell line (4T1); moreover, as an in vivo treatment of tumors, the FA-L-PEGPCL-TMX-QUER exhibited a clear tumor-inhibiting effect; therefore, according to this results, we can conclude that The FA-L-PEG-PCL-TMX-QUER NCs had a considerable potential for oral delivery of combination drugs having most clinical application.

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