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1.
Tailoring the Chemical Modification of Chitosan Hydrogels to Fine-Tune the Release of a Synergistic Combination of Chemotherapeutics.
Schneible, JD, Singhal, A, Lilova, RL, Hall, CK, Grafmüller, A, Menegatti, S
Biomacromolecules. 2019;(8):3126-3141
Abstract
Combination chemotherapy with a defined ratio and sequence of drug release is a clinically established and effective route to treat advanced solid tumors. In this context, a growing body of literature demonstrates the potential of hydrogels constructed with chemically modified polysaccharides as depots for controlled release of chemotherapeutics. Identifying the appropriate modification in terms of physicochemical properties of the functional group and its degree of substitution (χ) to achieve the desired release profile for multiple drugs is, however, a complex multivariate problem. To address this issue, we have developed a computational toolbox that models the migration of a drug pair through a hydrated network of polysaccharide chains modified with hydrophobic moieties. In this study, we chose doxorubicin (DOX) and Gemcitabine (GEM) as model drugs, as their synergistic effect against breast cancer has been thoroughly investigated, and chitosan as the model polymer. Our model describes how the modification of chitosan chains with acetyl, butanoyl, and heptanoyl moieties at different values χ governs both the structure of the hydrogel network and drug migration through it. Our experimental data confirm the in silico predictions for both single- and dual-drug release and, most notably, the counterintuitive inversion of release vs χ that occurs when switching from a single- to a dual-drug system. Consensus between predicted and experimental data indicates that acetyl modifications (χ = 32-42%) and butanoyl modifications (χ = 19-24%) provide synergistic GEM/DOX release molar ratios (i.e., 5-10). Collectively, these results demonstrate the potential of this model in guiding the design of chemotherapeutic hydrogels to combat cancer.
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2.
Separation of anthocyanins extracted from red cabbage by adsorption onto chitosan films.
Carvalho, VVL, Gonçalves, JO, Silva, A, Cadaval, TR, Pinto, LAA, Lopes, TJ
International journal of biological macromolecules. 2019;:905-911
Abstract
Anthocyanin pigments are suitable as natural dyes for food, cosmetics and dietary supplements, due to the demand for healthier products and their antioxidant properties. This work aimed to extract the anthocyanin pigments from red cabbage and its separation of the solution by adsorption operation onto chitosan films. The anthocyanin was extracted from red cabbage in water hot at 90 °C by 15 min. Chitosan was obtained from shrimp waste, and its films were produced by casting technique (tensile strength of 25.1 ± 1.9 MPa, elongation of 10.5 ± 3.5% and thicknesses of 103.1 ± 1.3 μm). The anthocyanin adsorption assays were performed in batch, and the highest adsorption capacity was around 140 mg g-1. The equilibrium experimental data were adjusted by Henry, Langmuir and Freundlich models, and all models showed a good fitting (R2 ≥ 0.96 and ARE ≤ 6.5%). The thermodynamic parameters represented endothermic and physical adsorption. The kinetic behavior was evaluated by empirical models, being the pseudo-first order model that showed the best fitting (R2 ≥ 0.97 and ARE ≤ 8.5%). This work presented suitable information about the anthocyanin molecules immobilization onto chitosan films and, these results could be important to the use these pigments with chitosan in different areas.
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3.
Chitosan enhances calcium carbonate precipitation and solidification mediated by bacteria.
Nawarathna, THK, Nakashima, K, Kawasaki, S
International journal of biological macromolecules. 2019;:867-874
Abstract
Formation of the biominerals in living organisms is mainly associated with organic macromolecules. These organic materials play an important role in the nucleation, growth, and morphology controls of the biominerals. Current study mimics this concept of organic matrix- mediated biomineralization by using microbial induced carbonate precipitation (MICP) method in combination with the cationic polysaccharide chitosan. CaCO3 precipitation was performed by the hydrolysis of urea by the ureolytic bacteria Pararhodobacter sp. SO1 in the presence of CaCl2, with and without chitosan. The crystal polymorphism and morphology of oven-dried samples were analyzed by X-ray diffraction and scanning electron microscopy. The amount of precipitate obtained was higher in the presence of chitosan. The precipitate included both of the CaCO3 and the chitosan hydrogel. Rhombohedral crystals were dominant in the precipitate without chitosan and distorted crystal agglomerations were found with chitosan. Sand solidification experiments were conducted in the presence of chitosan under different experimental conditions. By adding chitosan, more strongly cemented sand specimens could be obtained than those from conventional method. All of these results confirm the positive effect of chitosan for the CaCO3 precipitation and sand solidification.
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4.
Challenges and opportunities related to the use of chitosan as a food preservative.
Hu, Z, Gänzle, MG
Journal of applied microbiology. 2019;(5):1318-1331
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Abstract
Chitosan has attracted a growing attention as a food preservative due to its versatility, nontoxicity, biodegradability and biocompatibility. This review aims to provide a critical appraisal of the limitations and opportunities of the use of chitosan as a food preservative. The application of chitosan as a food preservative necessitates insights into mechanisms of chitosan-mediated cell death and injury, factors affecting chitosan activity and effects of chitosan on food safety and quality. Chitosan exerts antimicrobial activity by perturbing the negatively charged cell envelope of micro-organisms with its polycationic structure. Intrinsic characteristics, including molecular weight and degree of deacetylation (DD), and other ambient conditions, including pH, temperature and neighbouring components, affect chitosan activity. Because the antimicrobial activity of chitosan is mainly based on ionic interactions with negatively charged components of the bacterial cell envelope, the food matrix can strongly interfere with the antimicrobial activity of chitosan. Despite its limited antimicrobial efficacy, chitosan demonstrates both bactericidal and bacteriostatic effects in specific food products. Moreover, chitosan can also enhance the efficacy of commercial intervention technologies, such as heat and pressure treatment, and aid the preservation of food quality, including retardation of lipid oxidation, weight loss and deterioration in sensory attributes.
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Chitosan-based magnetic adsorbent for removal of water-soluble anionic dye: Artificial neural network modeling and molecular docking insights.
Cojocaru, C, Samoila, P, Pascariu, P
International journal of biological macromolecules. 2019;:587-599
Abstract
Herein, we report a new composite magnetic-adsorbent made of doped spinel ferrite (15%) dispersed throughout a matrix of chitosan (CS) cross-linked with glutaraldehyde (GA). The composite material was well characterized by using instrumental methods of physical-chemical analysis (SEM, EDX, FTIR and VSM). The produced adsorbent was applied for the removal of Acid Orange 7 (AO7) dye from aqueous solutions. Aspects of adsorption kinetics, isotherms and thermodynamics were detailed. According to the Dubinin-Radushkevich (D-R) isotherm, the mean free energy of adsorption ranged from 14.37 to 16.59 (kJ/mol), suggesting ion-exchange dominating phenomena. In addition, we developed an artificial neural network (ANN) model to explore extensively the effects of factors on the adsorption performance. The coupling of ANN model with a genetic algorithm provided optimal conditions of adsorption. A maximal color removal efficiency of 98.01% was observed experimentally under optimal conditions (pH 2.51, sorbent dosage 3.88 g/L, initial dye concentration 25.3 mg/L, contact time 204 min). To unveil interaction mechanism, we employed molecular docking simulations. Computational outcomes suggested the formation of hydrophobic contacts and hydrogen bonds between AO7 dye molecule and CS-GA receptor. Molecular docking results agreed with the D-R isotherm findings, highlighting that electrostatic forces were greater than Van-der-Waals interactions.
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Application of diethylenetriamine grafted on glyoxal cross-linked chitosan composite for the effective removal of metal ions in batch system.
Igberase, E, Osifo, PO
International journal of biological macromolecules. 2019;:1145-1155
Abstract
This investigation studied the removal of Cu2+, Pb2+, Cd2+, Zn2+, Ni2+ and Cr6+ ions from synthesised wastewater using modified chitosan macromolecules. On this note, chitosan beads (CS) were prepared and cross-linked with glyoxal solution. It was found that cross-linking increased the beads mechanical strength and chemical stability in acid solution and also increased the crystallinity of the beads in the process, which is a shortcoming, as the beads tend to have reduced adsorption capacity. To reduce this shortcoming, the cross-linked chitosan beads (DCS) were grafted with diethylenetriamine. The beads were characterised prior to adsorption studies. The amine concentration of the grafted cross-linked beads (GDCS) was observed to be nearly the same as the adsorption capacity (qmax); this concludes that the amine group of chitosan are the main reactive group. Also, the qmax was found to be 6.3 mmol/g with a 44.2% degree of grafting. The kinetics of the adsorption process was described reasonably well with the Swan model, where the experimental and simulated data were in close agreement. The effective diffusion coefficients (Deff) obtained by fitting the model to experimental data were found to be between 2.25·10-10 to 2.50·10-10 for Cu2+, Pb2+, Cd2+, Zn2+, Ni2+ and Cr6+ adsorption unto GDCS.
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Treatment of brittle nail with a hydroxypropyl chitosan-based lacquer, alone or in combination with oral biotin: A randomized, assessor-blinded trial.
Chiavetta, A, Mazzurco, S, Secolo, MP, Tomarchio, G, Milani, M
Dermatologic therapy. 2019;(5):e13028
Abstract
We evaluated in a randomized, assessor-blinded, study the efficacy of a hydroxypropyl chitosan-based nail lacquer (HPC-NL) alone or in combination with oral biotin (HPC-NL + B) in the treatment of brittle nail syndrome (BNS). Fifty subjects (21 men; mean age 64 years) with BNS were enrolled. Twenty-six were randomly assigned to HPC-NL and 24 to the HPC-NL and biotin, 10 mg/daily (+B). Topical and oral treatments lasted for 4 consecutive months. The primary outcome was the evolution of the Onychodystrophy Global Severity Score (OGSS) assessing nail dystrophy, lamellar and longitudinal splitting, dyschromia, and pitting. At baseline, the OGSS, mean (SD), was 8.4 (2.1) in the HPC-NL group and 11.8 (2.3) in the HPC-NL + B group. The OGSS was significantly reduced during treatments in both groups. At Month 4, OGSS was reduced by 57% (HPC-NL) and 62% (HPC-NL + B). At the end of study period, the percentage of subjects with an OGSS reduction of ≥50% in comparison with baseline was 53% in the HPC-NL group and 80% in the HPC-NL + B group (p = .05). Both treatments were well tolerated. In subjects with BNS, HPC-NL alone is associated with a clinically relevant improvement of nail appearance. The combination of HPC-NL and oral biotin is associated with further clinical improvement.
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Fabrication of biocomposite scaffolds made with modified hydroxyapatite inclusion of chitosan-grafted-poly(methyl methacrylate) for bone tissue engineering.
Tithito, T, Suntornsaratoon, P, Charoenphandhu, N, Thongbunchoo, J, Krishnamra, N, Tang, IM, Pon-On, W
Biomedical materials (Bristol, England). 2019;(2):025013
Abstract
In the present study, composite scaffolds of chitosan-graft-poly(methyl methacrylate) (Chi-g-PMMA) and mineral ions-loaded hydroxyapatite (mHA) (obtained by the hydrothermal treatment of hydroxyapatite (HA) in a simulated body fluid (SBF) solution (mHA@Chi-g-PMMA)) were prepared by the blending method. The physical properties, bioactivity, biological properties and their capabilities for sustained drug and protein release were studied. Physicochemical analysis showed a successful incorporation of the mineral ions in the HA particles and a good distribution of the mHA within the Chi-g-PMMA polymer matrix. The compressive strength and the Young's modulus were 15.760 ± 0.718 and 658.452 ± 17.020 MPa, respectively. In bioactivity studies, more apatite formation on the surface were seen after immersion in the SBF solution. In vitro growth experiments using UMR-106 osteoblast-like cells on the mHA@Chi-g-PMMA scaffold case showed that the attachment, viability and proliferation of the cells on the scaffolds had improved after 7 d of immersion. The in vitro release of two compounds (the cancer drug, doxorubicin (DOX)) and bovine serum albumin (BSA)), which had been attached to separate mHA@Chi-g-PMMA scaffolds, were studied to determine their suitability as drug delivery vehicles. It was found that the sustained release of DOX was 73.95% and of BSA was 57.27% after 25 h of incubation. These experimental results demonstrated that the mHA@Chi-g-PMMA composite can be utilized as a scaffold for bone cells ingrowth and also be used for drug delivery during the bone repairing.
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Chitosan Film as Eco-Friendly and Recyclable Bio-Adsorbent to Remove/Recover Diclofenac, Ketoprofen, and their Mixture from Wastewater.
Rizzi, V, Romanazzi, F, Gubitosa, J, Fini, P, Romita, R, Agostiano, A, Petrella, A, Cosma, P
Biomolecules. 2019;(10)
Abstract
This paper reported the first example on the use of chitosan films, without further modification, to remove and recover, through bio-sorption processes, the emerging pollutant Diclofenac from water. The latter was adopted as a model, among non-steroidal anti-inflammatory drugs, by obtaining a maximum adsorption capacity, qmax, on chitosan of about 10 mg/g, under the applied experimental conditions of work. The literature gap about the use of chitosan films, which was already used for dyes and heavy metals removal, to adsorb emerging pollutants from water was covered, claiming the wide range application of chitosan films to remove a different class of pollutants. Several parameters affecting the Diclofenac adsorption process, such as the pH and ionic strength of solutions containing Diclofenac, the amount of the bio-sorbent and pollutant, and the temperature values, were investigated. The kinetics and the adsorption isotherms, along with the thermodynamic parameters (ΔG°, ΔH°, and ΔS°) were also evaluated. The process occurred very efficiently, and Chitosan/Diclofenac amounts dependent, remove about the 90% of the pollutant, in 2 h, from the tested solutions, through electrostatic interaction involving the carboxylic moiety of Diclofenac and Chitosan amino groups. This finding was confirmed by the pH and salt effects on the bio-sorption process, including swelling measurements of Chitosan films and by FTIR-ATR analysis. In detail, the maximum adsorption was observed at pH 5, when pollutant and Chitosan were negatively and positively charged, respectively. By reducing or increasing the pH around this value, a reduced affinity was observed. Accordingly, the presence of salts retarded the Diclofenac removal screening its charges, which hinders the interaction with Chitosan. The sorption was spontaneous (ΔG° < 0) and endothermic (ΔH° > 0) following the pseudo-second order kinetic model. The process was Diclofenac and Chitosan amount dependent. In addition, the Freundlich and Temkin isotherms well described the process, which showed the heterogeneous character of the process. Experiments of the complete desorption were also performed by using NaCl solutions 0.25 M (like sea water salt concentration) proposing the reuse of the pollutant and the recycling of the bio-sorbent lowering the associated costs. The versatility of the adsorbent was reported by exploring the possibility to induce the Diclofenac light-induced degradation after the adsorption and by-products adsorption onto chitosan films. To emphasize the chitosan capacity of treating water, the removal of another pollutant such as Ketoprofen and the mixture of Diclofenac and Ketoprofen were investigated. In this way, a green and eco-friendly production-pollution prevention technology for removing emerging pollutants from water was presented, which reduced the overall environmental impact. This illustrated experiments both in static and dynamic conditions for potential industrial applications.
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Nanostructured Chitosan-Based Biomaterials for Sustained and Colon-Specific Resveratrol Release.
Iglesias, N, Galbis, E, Díaz-Blanco, MJ, Lucas, R, Benito, E, de-Paz, MV
International journal of molecular sciences. 2019;(2)
Abstract
In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box⁻Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79⁻81%), and the CTS-NPs composites (29⁻34%).