Assessment of arsenic-induced modifications in the DNA methylation of insulin-related genes in rat pancreatic islets.

Extended exposure to inorganic arsenic through contaminated drinking water has been linked with increased incidence of diabetes mellitus. The most common exposure occurs through the consumption of contaminated drinking water mainly through geogenic sources of inorganic arsenic. Epigenetic modifications are important mechanisms through which environmental pollutants could exert their toxic effects. Bisulfite sequencing polymerase chain reaction method followed by Sanger sequencing was performed for DNA methylation analysis. Our results showed that sodium arsenite treatment significantly reduced insulin secretion in pancreatic islets. It was revealed that the methylation of glucose transporter 2 (Glut2) gene was changed at two cytosine-phosphate-guanine (CpG) sites (-1743, -1734) in the promoter region of the sodium arsenite-treated group comparing to the control. No changes were observed in the methylation status of peroxisome proliferator-activated receptor-gamma (PPARγ), pancreatic and duodenal homeobox 1 (Pdx1) and insulin 2 (Ins2) CpG sites in the targeted regions. Measuring the gene expression level showed increase in Glut2 expression, while the expression of insulin (INS) and Pdx1 were significantly affected by sodium arsenite treatment. This study revealed that exposure to sodium arsenite changed the DNA methylation pattern of Glut2, a key transporter of glucose entry into the pancreatic beta cells (ß-cells). Our data suggested possible epigenetic-mediated toxicity mechanism for arsenite-induced ß-cells dysfunction. Further studies are needed to dissect the precise epigenetic modulatory activity of sodium arsenite that affect the biogenesis of insulin.

Synthesis and characterization of chitosan/carbon quantum dots/Fe2O3 nanocomposite comprising curcumin for targeted drug delivery in breast cancer therapy.

Curcumin, a natural compound with promising anti-cancerous features, suffers from a number of shortcomings such as low chemical stability, bioavailability, and solubility, which impedes its application as an alternative for conventional cancer therapy. In this study, curcumin comprising Fe2O3/Chitosan/CQDs was fabricated through double emulsion method (W/O/W) for the first time to exploit its anticancer features while alleviating its limitation, making this nanocomposite promising in targeted drug delivery. Chitosan, a hydrophilic biopolymer, has incorporated to constitute an adhesive pH-sensitive matrix that can trap the hydrophobic drug resulting in controlled drug release in cancerous environment. Carbon quantum dots render luminescence and water solubility properties, which is favorable for tracing drug release and bio imaging along with enhancement of biocompatibility. Fe2O3 can improve chemical stability and bioavailability in addition to anti-cancerous property. XRD and FTIR analysis confirmed the physical interaction between the drug and fabricated nano composite in addition to chemical bonding between the prepared nano composite. Matrix and spherical structure of the formed drug is corroborated by FESEM analysis. DLS analysis' results determine the mean size of the nano composite at about 227.2 nm and zeta potential result is indicative of perfect stability of the fabricated drug. Various kinetic models for drug release were fitted to experimental data in order to investigate the drug release in which Korsmeyer-Peppas' model was the predominant release system in cancerous environment. In vitro studies through flow cytometry and MTT assay exerted noticeable cytotoxicity effect on MCF-7 cell lines. It can be deduced from these results that curcumin encapsulated with CS/CQDs/Fe2O3 nanocomposites is an excellent alternative for targeted drug delivery.

Synthesis and characterization of a novel, pH-responsive sustained release nanocarrier using polyethylene glycol, graphene oxide, and natural silk fibroin protein by a green nano emulsification method to enhance cancer treatment.

In this study, for the first time, by employing a simple and efficient double nano-emulsification method and using sweet almond oil as the organic phase, polyethylene glycol (PEG)/graphene oxide (GO)/silk fibroin (SF) hydrogel-nanocomposite was synthesized. The aim of the research was to fabricate a biocompatible targeted pH-sensitive sustained release carrier, improve the drug loading capacity and enhance the anticancer effect of doxorubicin (DOX) drug. The obtained values for the entrapment (%EE) and loading efficacy (%LE) were 87.75 ± 0.7 % and 46 ± 1 %, respectively, and these high values were due to the use of GO with a large specific surface area and the electrostatic interaction between the drug and SF. The Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses confirmed the presence of all the components in the nanocomposite and the suitable interaction between them. Based on the results of dynamic light scattering analysis (DLS) and zeta potential analysis, the mean size of the carrier particles and its surface charge were 293.7 nm and -102.9 mV, respectively. The high negative charge was caused by the presence of hydroxyl groups in GO and SF and it caused proper stability of the nanocomposite. The spherical core-shell structure with its homogeneous surface was also observed in the field emission scanning electron microscopy (FE-SEM) image. The cumulative release percentage of the nanocarrier reached 95.75 after 96 h and it is higher in the acidic environment at all times. The results of fitting the release data to the kinetic models suggested that the mechanism of release was dissolution-controlled anomalous at pH 7.4 and diffusion-controlled anomalous at pH 5.4. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry showed an increase in toxicity on MCF-7 cells and improved apoptotic cell death compared to the free drug. Consequently, the findings of this research introduced and confirmed PEG/GO/SF nanocomposite as an attractive novel drug delivery system for pH-sensitive and sustained delivery of chemotherapeutic agents in biomedicine.

Synthesis and characterization of chitosan/polyvinylpyrrolidone coated nanoporous γ-Alumina as a pH-sensitive carrier for controlled release of quercetin.

pH-sensitive drug delivery systems based on amphiphilic copolymers constitute a promising strategy to overcome some challenges to cancer treatment. In the present study, quercetin-loaded chitosan/polyvinylpyrrolidone/γ-Alumina nanocomposite was fabricated through a double oil in water emulsification method for the first time. γ-Alumina was incorporated to improve the drug loading efficiency and release behavior of polyvinylpyrrolidone and chitosan copolymeric hydrogel. γ-Alumina nanoparticles were obtained by the sol-gel method with a nanoporous structure, high surface area, and hydroxyl-rich surface. Quercetin, a natural anticancer agent, was loaded into the nanocomposite as a drug model. XRD and FTIR analyses confirmed the crystalline properties and chemical bonding of the prepared nanocomposite. The size of drug-loaded nanocomposites was 141 nm with monodisperse particle distribution, having a spherical shape approved by DLS analysis and FE-SEM, respectively. Incorporating γ-Alumina nanoparticles improved the encapsulation efficiency up to 95%. Besides, swelling study and the quercetin release profile demonstrated that γ-Alumina ameliorated pH sensitivity of nanocomposite and a targeted controlled release was obtained. Various release kinetic models were applied to the experimental release data to study the mechanism of drug release. Through MTT assay and flow cytometry, the quercetin-loaded nanocomposite showed significant cytotoxicity on MCF-7 breast cancer cells. Also, the enhanced apoptotic cell death confirmed the anticancer activity of γ-Alumina. These results suggest that the chitosan/polyvinylpyrrolidone/γ-Alumina nanocomposite is a novel pH-sensitive drug delivery system for anticancer applications.

Preparation of pH-sensitive chitosan/polyvinylpyrrolidone/α-Fe2O3 nanocomposite for drug delivery application: Emphasis on ameliorating restrictions.

Chitosan (CS)/polyvinylpyrrolidone (PVP)/hematite (α-Fe2O3) nanocomposites loaded with Doxorubicin (drug model) were synthesized via an oil-in-water emulsification method to develop a biocompatible and pH-sensitive drug nanocarrier for the first time. A hydrogel, including CS, PVP, and α-Fe2O3, was fabricated successfully with glutaraldehyde (GA) as the cross-linker. Incorporating α-Fe2O3 into CS/PVP hydrogel improved the pH-sensitivity and developed beneficial hydrogel. FTIR and XRD analysis illustrated physical interactions between polymer-polymer, polymer-drug, and crystalline behavior of prepared nanocomposite. These analyses also confirmed chemical bonding in nanocomposite's structure. The FE-SEM analysis showed successful impregnation of α-Fe2O3 into CS/PVP matrix and spherical structure. To clarify the size distribution and surface charge of the drug-loaded nanocomposite (CS/PVP/α-Fe2O3/Dox), DLS and zeta analyses were conducted. They showed the mean size of nanocomposites at about 247 nm. Drug-loaded CS/PVP/α-Fe2O3 nanocomposite and CS/PVP/Dox were studied for their release behavior and kinetics. Furthermore, the effect of α-Fe2O3 on release from CS/PVP/α-Fe2O3/Dox nanocomposite was investigated. That showed an increase in encapsulation of Doxorubicin and beneficial release behavior such as slow-release and retention effect. The release from this drug-loaded nanocomposite revealed excellent pH-sensitive and controlled release of the drug. Besides, the in vitro cytotoxicity and cell apoptosis were studied to recognize biological properties. These analyses revealed that drug-loaded nanocomposite caused high inhibition to MCF-7 cells in presence of α-Fe2O3 and proved the hematite's anti-cancer effect. By and large, this study confirmed CS/PVP/α-Fe2O3 nanocomposites as a potential candidate for the controlled pH-sensitive release of the drug.