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A free radical polymerization method was adopted for the fabrication of hybrid hydrogel films based on acrylamide and polyethylene glycol dimethacrylate as plasticizing and crosslinking agents, respectively, to be employed as smart skin bandages. Electro-sensitivity, biocompatibility and proteolytic properties were conferred to the final polymer networks by introducing graphene oxide (0.5% w/w), gelatin or trypsin (10% w/w) in the polymerization feed. The physical chemical and mechanical characterization of hybrid materials was performed by means of determination of protein content, Raman spectroscopy, thermogravimetric analysis and measurement of tensile strength. The evaluation of both water affinity and curcumin release profiles (analyzed by suitable mathematical modelling) upon application of an external electric stimulation in the 0-48 voltage range, confirmed the possibility to modulate the release kinetics. Proper proteolytic tests showed that the trypsin enzymatic activity was retained by 80% upon immobilization. Moreover, for all samples, we observed a viability higher than 94% in normal human fibroblast cells (MRC-5), while a reduction of methicillin-resistant Staphylococcus aureus CFU mL -1 (90%) was obtained with curcumin loaded samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Many tumors including prostate cancer are maintained by cancer stem cells (CSCs), which might cause tumor relapse if not eradicated during the course of treatment. Specific targeting or radiosensitization of CSCs bear promise to improve tumor curability by synergistic effects in combination with radiotherapy. Carbon nanotubes (CNTs) can be used as promising drug delivery systems for anticancer drugs such as the flavonoid catechin. Catechin is an extensively studied active ingredient of the different plants, including green tea, and it is widely recognized as co-adjuvant in cancer therapy. Here we describe the synthesis of biocompatible, catechin-loaded and gelatin-conjugated CNTs (Gel_CT_CNTs) with anticancer properties and demonstrate their potential for the eradication of prostate CSCs in combination with X-ray irradiation. Gel_CT_CNTs showed a significant enhancement of in vitro anticancer activity as compared to catechin alone. Moreover, treatment of prostate cancer cells with Gel_CT_CNT nanohybrids inhibited the tumorigenic cell population defined by a high aldehyde dehydrogenase (ALDH) activity. A combination of X-ray irradiation and treatment with Gel_CT_CNTs caused a decrease in the protein level of stem cell-related transcription factors and regulators including Nanog, Oct4 and β-catenin and led to an increase of cancer cell radiosensitivity as demonstrated by clonogenic and spherogenic cell survival assays. Taken together, our results suggest that a combination of irradiation and Gel_CT_CNTs can be potentially used for the radiosensitization and eradication of prostate CSC populations., (© 2015 UICC.)

Purpose: Preparation of Nanographene oxide (NGO) - Gelatin hybrids for efficient treatment of Neuroblastoma., Methods: Nanohybrids were prepared via non-covalent interactions. Spectroscopic tools have been used to discriminate the chemical states of NGO prior and after gelatin coating, with UV visible spectroscopy revealing the maximum binding capacity of gelatin to NGO. Raman and X-ray photoelectron spectroscopy (XPS) demonstrated NGO and Gelatin_NGO nanohybrids through a new chemical environments produced after noncovalent interaction. Microscopic analyses, atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to estimate the thickness of samples and the lateral width in the nanoscale, respectively., Results: The cell viability assay validated Gelatin_NGO nanohybrids as a useful nanocarrier for Carboplatin (CP) release and delivery, without obvious signs of toxicity. The nano-sized NGO (200 nm and 300 nm) did not enable CP to kill the cancer cells efficiently, whilst the CP loaded Gel_NGO 100 nm resulted in a synergistic activity through increasing the local concentration of CP inside the cancer cells., Conclusions: The nanohybrids provoked high stability and dispersibility in physiological media, as well as enhanced the anticancer activity of the chemotherapy agent Carboplatin (CP) in human neuroblastoma cells.

Novel spherical hybrid hydrogels composed of gelatin and multi-walled carbon nanotubes were synthesized by emulsion polymerization in the presence of sodium methacrylate and N,N'-ethylenebisacrylamide, and proposed as drug delivery microspheres for the electro-responsive release of Diclofenac sodium salt. Different amounts of nanotubes (up to 35% by weight) were covalently inserted into the polymeric network in order to determine the percentage conferring the highest electric sensitivity to the composite microspheres. Characterization of hydrogels was performed by electrical, morphological and calorimetric analyses, Raman measurements, biocompatibility assays and evaluation of the swelling behaviors in water (pH 1.0 and pH 7.4) with and without the application of an external electric field. Finally, the release profiles were determined and the diffusion behavior was evaluated by semi-empirical equations., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A new hybrid material made of gelatin, catechin and carbon nanotubes was prepared by the non-covalent incorporation of carbon nanotubes (CNTs) into a gelatin-catechin covalent conjugate. The composite materials was tested by means of determination of the dispersion stability in water and the functionalization degree was assessed by the Folin-Ciocalteu method, finding a 0.9 mg of CT/g of protein conjugate. Subsequently, the complete retention of the antioxidant properties of the flavonoid after incorporation into the composite was proved by DPPH and ABTS assays and IC50 values of 5.74 mg mL(-1) and 0.39 mg mL(-1) were recorded. The presence of CNT into the materials did not interfere with the scavenging activities of the catechin. Finally, the anticancer activity on HeLa cancer cells was evaluated and a considerable increase in the therapeutic activity of the flavonoid was recorded moving from the free to the conjugated form in the presence of CNT, while in absence of CNT a reduction of the efficiency was observed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Hybrid hydrogel films able to modulate the release of anionic species, ketoprofen (Ket) and bovine serum albumin (BSA), as a function of their molecular size are prepared by UV-induced polymerization of methacrylated gelatin in the presence of oxidized multiwalled carbon nanotubes (MWNT_COOH). The dual-stimuli responsive composites can modulate the release in response to the variation of temperature and the application of an external voltage. Drug release profiles, analyzed by mathematical models, show that different temperatures (25 and 45 °C) and applied voltages (0 and 36 V) have a different effect on the release of the two therapeutics. Ket release is enhanced at 45 °C (77% vs 22% at 25 °C) with the maximum value recorded when 36 V is applied (94%). An increase in the amount of released BSA is recorded at 45 °C (96% vs 50% at 25 °C), while the application of the external voltage reduces this value (39%). [ABSTRACT FROM AUTHOR]

Hybrid materials with enhanced antibacterial activity were prepared by incorporation of carbon nanotubes within gelatin-fluoroquinolones bioconjugates. Gelatin bioconjugates were characterized by UV-Vis, FT-IR, and calorimetric analyses, nanohybrids by morphological analyses. Biocompatibility was evaluated on human mesenchymal stem cells, and antibacterial performance againstKlebsiella pneumoniaeandEscherichia coli. Minimun inhibitory concentrations from 0.025 to 0.05 µg mL−1and from 0.025 to 0.10 µg mL−1, and MBC from 0.025 to 0.10 µg mL−1and from 0.05 to 0.20 µg mL−1were detected forEscherichia coliandKlebsiella pneumoniae, respectively, showing that nanotubes increase antimicrobial activity comparing to both free and gelatin-conjugated drugs. [ABSTRACT FROM AUTHOR]

Native gelatin, N, N′-ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100-500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug-polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations. [ABSTRACT FROM AUTHOR]

Monodispersed polymersomes based on a hydrophobically-modified protein with dimensional range between 154 and 254 nm were prepared employing a water addition/solvent evaporation method. Gelatin hydrolyzate and PEG 40 -stearate, acting as hydrophilic and hydrophobic blocks, respectively, underwent radical coupling and three materials with different hydrophilic/lipophilic ratio were obtained by varying the amount of PEG 40 -stearate in the reaction feed. Critical aggregation concentrations of each amphiphilic polymer were found ranged from 3.9 to 10.2 μg mL −1 , with lower values recorded for conjugate with lower hydrophilic/lipophilic ratio. Anticancer drug methotrexate was loaded into the vesicular systems with efficiency strictly dependent on the gelatin hydrolyzate content and the in vitro releasing profile assessed and analyzed by suitable mathematical models. To prove the applicability of the proposed delivery vehicle, the biocompatibility properties were assessed in normal human lung fibroblasts cells MRC-5, while the anticancer efficiency was tested on H1299 lung cancer cells, proving that the drug encapsulation into the polymersomes dramatically reduced the cytotoxicity on healthy cells while preserving its efficiency in killing cancer cells. [ABSTRACT FROM AUTHOR]

We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The anticancer potential of the resulting nanohybrid was validated on an aggressive melanoma cell line, in vitro and in zebrafish xenotransplants. The nanohybrid strongly enhances the cytotoxic effect of (+)-catechin. At a concentration of (+)-catechin 50 μg/ml, the nanohybrid inhibited the ability of melanoma cells to proliferate (100% increase of cell doubling time and severe impairment in zebrafish xenotransplants), to migrate (totally inhibition in vitro and 50% reduction of cell motility in zebrafish xenotransplants) and to induce neo-angiogenesis (100% inhibition in zebrafish xenotransplants). Conversely, the free (+)-catechin and carrier (CNT:gel) had no statistically significant effects over the control, at any concentration tested. Our results suggest that the use of the nanohybrid, able to improve the therapeutic efficacy of the catechins, could represent a successful strategy for a future clinical translation. [ABSTRACT FROM AUTHOR]