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Ameliorating Quercetin Constraints in Cancer Therapy With Ph-Responsive Agarose-Polyvinylpyrrolidone -Hydroxyapatite Nanocomposite Encapsulated in Double Nanoemulsion Publisher Pubmed



Samadi A1 ; Pourmadadi M1 ; Yazdian F2 ; Rashedi H1 ; Navaeinigjeh M3 ; Eufrasiodasilva T4, 5
Authors
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Authors Affiliations
  1. 1. Department of Biotechnology, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
  2. 2. Department of Life Science Engineering, Faculty of New Science and Technologies, University of Tehran, Tehran, Iran
  3. 3. Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Health Technology, Technical University of Denmark (DTU), Kgs. Lyngby, 2800, Denmark
  5. 5. Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Dentistry - Regenerative Biomaterials, Philips van Leydenlaan 25, Nijmegen, 6525EX, Netherlands

Source: International Journal of Biological Macromolecules Published:2021


Abstract

Despite quercetin (QC) promising features for cancer therapy, low solubility, poor permeability, and short biological half-life time significantly confine its application in cancer therapy. In this study, a novel approach is developed to improve loading efficiency and attain quercetin sustained-release concurrently. In this direction, hydrogel nanocomposite of agarose (AG)-polyvinylpyrrolidone (PVP)-hydroxyapatite (HAp) was loaded with QC. Incorporating HAp nanoparticles in the AG-PVP hydrogel improved the loading efficiency up to 61%. Also, the interactions between nanoparticle, drug, and hydrogel polymers rendered the nanocomposite pH-responsive at acidic conditions and controlled the burst release at neutral conditions. Then, QC-loaded hydrogel was encapsulated into the water in oil in water nanoemulsions to further sustain the drug release. As a result, the pH-responsive release of QC with prolonged-release over 96 h was observed. In more detail, according to the Korsmeyer-Peppas mathematical model, the mechanism of release was anomalous (diffusion-controlled) at pH 7.4 and anomalous transport (dissolution-controlled) at pH 5.4. The presence of all nanocomposite components was confirmed with FTIR analysis, and XRD results approved the incorporation of QC in the fabricated nanocomposite. The homogeneous surface of the nanocomposite in FESEM images showed good compatibility between components. The zeta potential analysis confirmed the good stability of the nanocarriers. Besides, the fabricated AG-PVP-HAp-QC platform showed significant cytotoxicity on MCF-7 cells compared to QC as a free drug (p < 0.001) and to quercetin-loaded AG-PVP (AG-PVP-QC) (p < 0.001) with enhanced apoptosis induction after the addition of HAp. Accordingly, this delivery platform ameliorated loading and sustained-release of QC, as well as its anticancer activity by releasing the drug at an effective therapeutic level over a long period to induce apoptosis. Thus, turning this drug delivery system into a potential candidate for further biomedical applications. © 2021
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