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Eur J Pharm Biopharm. 2017 Aug;117:324-332. doi: 10.1016/j.ejpb.2017.05.002. Epub 2017 May 4.

pH/redox dual-sensitive dextran nanogels for enhanced intracellular drug delivery.

Author information

1
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy. Electronic address: manuela.curcio@unical.it.
2
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, R+DPharma Group (GI-1645), Facultad de Farmacia, and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782-Santiago de Compostela, Spain.
3
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.

Abstract

pH/redox dual-responsive nanogels (DEX-SS) were prepared by precipitation polymerization of methacrylated dextran (DEXMA), 2-aminoethylmethacrylate (AEMA) and N,N'-bis(acryloyl)cystamine (BAC), and then loaded with methotrexate (MTX). Nanogels were spherical and exhibited homogeneous size distribution (460nm, PDI<0.30) as observed using dynamic light scattering (DLS) and scanning electron microscopy (SEM). DEX-SS were sensitive to the variations of pH and redox environment. Nanogels incubated in buffer pH 5.0 containing 10mM glutathione (GSH) synergistically increased the mean diameter and the PDI to 750nm and 0.42, respectively. In vitro release experiments were performed at pH 7.4 and 5.0 with and without GSH. The cumulative release of MTX in pH 5.0 medium with 10mMGSH was 5-fold higher than that recorded at pH 7.4 without GSH. Fibroblasts and tumor cells were used to tests the effects of blank DEX-SS and MTX@DEX-SS nanogels on cell viability. Remarkable influence of pH on nanogels internalization into HeLa cells was evidenced by means of confocal microscopy and flow cytometry.

KEYWORDS:

Cell uptake; Controlled drug release; Dextran; Flow cytometry; Stimuli-responsive nanogels; Tumor cells

PMID:
28478161
DOI:
10.1016/j.ejpb.2017.05.002
[Indexed for MEDLINE]

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