pH-Responsive therapeutic solid lipid nanoparticles for reducing P-glycoprotein-mediated drug efflux of multidrug resistant cancer cells

International Journal of Nanomedicine
Hsin-Hung ChenHsin-Cheng Chiu

Abstract

In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs) carrying doxorubicin (DOX) capable of overcoming multidrug resistance (MDR) breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100 nm and a low polydispersity index (under 0.20) with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 μM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membrane...Continue Reading

Citations

Jun 9, 2016·Colloids and Surfaces. B, Biointerfaces·Neeraj K GargOm Prakash Katare
May 28, 2016·Journal of Nanobiotechnology·Ewelina PiktelRobert Bucki
May 14, 2021·Frontiers in Chemistry·Neerupma DhimanGiriraj T Kulkarni

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Methods Mentioned

BETA
acylation
dynamic light scattering
transmission electronic microscopy
fluorescence spectroscopy
confocal microscopy
NMR
xenograft

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