Design of pH-responsive polymeric nanocarrier for targeted delivery of pyrogallol with enhanced antitumor potential in colon cancer.

PURPOSE: To synthesize a polymeric pH-sensitive nanocarrier for the delivery of pyrogallol and investigate the anti-tumor activity of pyrogallol-loaded polymeric nanogel against colon cancer in rats. METHODS: Poly(ethylene glycol)/polyacrylic acid (PEG/PAAc) nanogel was performed using gamma irradiation technique at irradiation doses; 30,40, and 50 kGy. The particle size distribution and diameter were investigated under the influence of various parameters by using dynamic light scattering analysis (DLS). The particle size was diminished by increasing AAc content and irradiation dose. Characterization of the performed nanogel was performed by (FT-IR) and (TEM). In vitro drug release behavior of the nanogel towards pyrogallol drug was assessed. Furthermore, the anti-cancer therapeutic efficiency of pyrogallol loaded PEG/PAAc nanogel was evaluated in a chemically induced colon cancer model in rats. RESULTS: Pyrogallol/PEG/PAAc significantly reduced tumor incidence and volume as compared to DMH group. Also, it activated apoptotic pathway via up-regulating Bax, cytochrome C, cleaved caspase-3, p53, and down-regulating Bcl-2 expression. Furthermore, it attenuated cell cycle progression via reducing Cyclin A, Cyclin D1, and Cyclin E expression. It exhibited anti-proliferative activity through inhibiting PI3K/AKT signaling and downregulating the phosphorylation of AKT. It reduced pro-inflammatory cytokines TNF-α and IL-6. Results were confirmed by histopathological examination of colonic tissue. Interestingly, pyrogallol/PEG/PAAc demonstrated anti-tumor potential more efficiently than free pyrogallol, revealing localized drug delivery. CONCLUSION: This formulation could be considered as a promising agent in the treatment of colon cancer.

Remediation of Astrazon blue and Lerui acid brilliant blue dyes from waste solutions using amphoteric superparamagnetic nanocomposite hydrogels based on chitosan prepared by gamma rays.

A nanocomposite hydrogel of chitosan/polypropenoic acid/ethylenediamine/magnetite (Cs/PPA/EDA/Fe3O4-NPs) was prepared using a gamma irradiation source (60Co). In the present study, chitosan/propenoic acid with different ratios and ethylenediamine were used as a matrix and Fe3O4 as a filler. The nanocomposite hydrogel was irradiated at 30 kGy using the γ-radiation technique as a crosslinking tool. The prepared nanocomposites were characterized utilizing several analytical techniques including Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM), and X-ray diffractometer (XRD). Results show that the Cs/PPA/EDA/Fe3O4-NPs nanocomposite has superabsorbent and superparamagnetic properties. The kinetic model of AB and LABB dyes adsorption onto the obtained nanocomposite hydrogel was confirmed and observed to be a pseudo-second-order reaction. The thermodynamic study proved that the adsorption process is endothermic in nature. The Langmuir plot best fitted the other isotherm models. The prepared Cs/PPA/EDA/Fe3O4-NPs nanocomposite hydrogel showed an excellent adsorption capacity for the removal of hazardous and toxic basic Astrazon blue (193.21 mg/g) and acidic Lerui Acid Brilliant Blue (51.9 mg/g) dyes from contaminated solutions. The results reveal that the Cs/PPA/EDA/Fe3O4-NPs nanocomposite hydrogel significantly removed the hazardous, toxic basic AB and acidic LABB dyes from waste solutions.

Synthesis, characterization and evaluation of resveratrol-loaded functionalized carbon nanotubes as a novel delivery system in radiation enteropathy.

Radiation-induced enteropathy is a major clinical challenge during radiotherapy. Resveratrol displays beneficial pharmacological activities; however, low oral bioavailability limits its effectiveness. This study aims at preparing methacrylic acid (MAAc) functionalized multi-walled carbon nanotubes (MWCNTs-MAAc) as carriers for pH triggered controlled release of resveratrol in an effort to improve the drug therapeutic potential. MWCNTs-MAAc were prepared using radiation technique and then characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), scanning electron microscope (SEM), X-ray diffraction (XRD) and Fourier transform-infrared (FT-IR) spectroscopy. In vitro drug release profile at different pH values was analyzed. Furthermore, the designed RES-MWCNTs-MAAc nanocomplex was evaluated against radiation-induced enteropathy in rats. Oral administration of RES-MWCNTs-MAAc restored colonic redox state and elevated antioxidant enzymes activities glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) and reduced colonic inflammatory mediators tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interferone-γ (IFN-γ) contents in addition to declining the intrinsic apoptotic pathway as evidenced by down-regulation of Bax and caspase-3 proteins expression accompanied by up-regulation of Bcl-2 protein expression. RES-MWCNTs-MAAc was more efficient than free resveratrol due to the delivery system that allowed prolonged resveratrol release at target site. Thus, this formulation could serve as a beneficial anti-inflammatory approach for patients during radiotherapy.

Radiation-synthesis of chitosan/poly (acrylic acid) nanogel for improving the antitumor potential of rutin in hepatocellular carcinoma.

The current study aimed to investigate the ability of chitosan/poly (acrylic acid) nanogel (CAN) to improve the bioavailability and anticancer potential of rutin. Synthesis of CAN was carried out by gamma radiation-induced polymerization of acrylic acid in an aqueous solution of chitosan. The relationship between the hydrodynamic radius of CAN and the absorbed radiation doses was also investigated. The prepared nanogels were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR) techniques, and then, it was used as a nano-drug carrier for rutin. The developed formulation was evaluated for its antitumor activity against chemically induced hepatocarcinoma in rats. The following parameters were measured: aspartate and alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, and total bilirubin as liver function test; vascular endothelial growth factor as an angiogenesis marker; α-fetoprotein as a tumor marker; and P53, caspase-3, Bax, and Bcl-2 as apoptosis markers. Histopathological examination was also confirmed. Significant enhanced anti-proliferative, anti-angiogenic, and apoptotic effects were observed for rutin-loaded CAN than free rutin, indicating that this formulation could provide a novel therapeutic approach to serve as a promising agent for treatment of hepatocellular carcinoma. Graphical abstract.