Therapeutic applications of sustainable new chitosan derivatives and its nanocomposites: Fabrication and characterization.

Chitosan (CS) is a biologically active biopolymer used in different medical applications due to its biodegradability, biocompatibility, and nontoxicity. Nanotechnology is an exciting and quick developing field in medical applications. Nanoparticles have shown great potential in the treatment of cancer and inflammation. In the present work modification of chitosan and its (Ag, Au, or ZnO) nanocomposites by N-aminophthalimide (NAP) occurred through the reaction with epichlorohydrin (ECH) as a crosslinker in the presence or absence of glutaraldehyde (GA) under different reaction conditions using microwave irradiation to give modified chitosan derivatives CS-2, CS-6, and their nanocomposites. Modified chitosan derivatives were characterized using different tools. CS-2 and CS-6 derivatives displayed enhancement of thermal stability and crystallinity compared to chitosan. Additionally, CS-2, CS-6, and their nanocomposites exhibited improvements in antitumor activity against HeLa cancer cells and enzymatic inhibitory against trypsin and α-chymotrypsin enzymes compared to chitosan. However, CS-2 revealed the highest cell growth inhibition% toward HeLa cells (89.02 ± 1.46 %) and the enzymatic inhibitory toward α-chymotrypsin enzyme (17.13 ± 1.59 %). Furthermore, CS-Au-2 showed the highest enzymatic inhibitory against trypsin enzyme (28.14 ± 1.76 %). These results suggested that the new chitosan derivatives CS-2, CS-6, and their nanocomposites could be a platform for medical applications against HeLa cells, trypsin, and α-chymotrypsin enzymes.

New sustainable antimicrobial chitosan hydrogels based on sulfonamides and its nanocomposites: Fabrication and characterization.

Chitosan (Ch), a linear cationic biopolymer, has broad medical applications. In this paper, new sustainable hydrogels (Ch-3, Ch-5a, Ch-5b) based on chitosan/sulfonamide derivatives 2-chloro-N-(4-sulfamoylphenethyl) acetamide (3) and/or 5-[(4-sulfamoylphenethyl) carbamoyl] isobenzofuran-1,3-dione (5) were prepared. Hydrogels (Ch-3, Ch-5a, Ch-5b) were loaded (Au, Ag, ZnO) NPs to form its nanocomposites to improve the antimicrobial efficacy of chitosan. The structures of hydrogels and its nanocomposites were characterized using different tools. All hydrogels displayed irregular surface morphology in SEM, however hydrogel (Ch-5a) revealed the highest crystallinity. The highest thermal stability was shown by hydrogel (Ch-5b) compared to chitosan. The nanocomposites represented nanoparticle sizes <100 nm. Antimicrobial activity was assayed for hydrogels using disc diffusion method exhibited great inhibition growth of bacteria compared to chitosan against S. aureus, B. subtilis and S. epidermidis as Gram-positive, E. coli, Proteus, and K. pneumonia as Gram-negative and antifungal activity against Aspergillus Niger and Candida. Hydrogel (Ch-5b) and nanocomposite hydrogel (Ch-3/Ag NPs) showed higher colony forming unit (CFU) and reduction% against S. aureus and E. coli reaching 97.96 % and 89.50 % respectively in comparison with 74.56 % and 40.30 % for chitosan respectively. Overall, fabricated hydrogels and its nanocomposites enhanced the biological activity of chitosan and it can be potential candidates as antimicrobial drugs.

New potential anti-SARS-CoV-2 and anti-cancer therapies of chitosan derivatives and its nanoparticles: Preparation and characterization.

Chitosan (CS) is a biopolymer and has reactive amine/hydroxyl groups facilitated its modifications. The purpose of this study is improvement of (CS) physicochemical properties and its capabilities as antiviral and antitumor through modification with 1-(2-oxoindolin-3-ylidene)thiosemicarbazide (3A) or 1-(5-fluoro-2-oxoindolin-3-ylidene)thiosemicarbazide (3B) via crosslinking of poly(ethylene glycol)diglycidylether (PEGDGE) using microwave-assisted as green technique gives (CS-I) and (CS-II) derivatives. However, (CS) derivatives nanoparticles (CS-I NPs) and (CS-II NPs) are synthesized via ionic gelation technique using sodium tripolyphosphate (TPP). Structures of new (CS) derivatives are characterized using different tools. The anticancer, antiviral efficiencies and molecular docking of (CS) and its derivatives are assayed. (CS) derivatives and its nanoparticles show enhancement in cell inhibition toward (HepG-2 and MCF-7) cancer cells in comparison with (CS). (CS-II NPs) reveals the lowest IC50 values are 92.70 ± 2.64 µg/mL and 12.64 µ g/mL against (HepG-2) cell and SARS-CoV-2 (COVID-19) respectively and the best binding affinity toward corona virus protease receptor (PDB ID 6LU7) -5.71 kcal / mol. Furthermore, (CS-I NPs) shows the lowest cell viability% 14.31 ± 1.48 % and the best binding affinity -9.98 kcal/moL against (MCF-7) cell and receptor (PDB ID 1Z11) respectively. Results of this study demonstrated that (CS) derivatives and its nanoparticles could be potentially employed for biomedical applications.

New chitosan derivatives inspired on heterocyclic anhydride of potential bioactive for medical applications.

In the present work new chitosan derivatives inspired heterocyclic anhydride were prepared to improve the biological activities of chitosan via imidization reaction of chitosan (CS) and N-(1,3-dioxoisoindolin-2-yl)-1,3-dioxo-1,3-dihydroiso-benzofuran-5-carboxamide (5) to yield amic acid CS-6 at room temperature and imide CS-8 thermally. However, the reaction between (CS) and anhydride (5) in presence of sodium tripolyphosphate (TPP) or Poly (ethylene glycol) diglycidyl ether (PEGDG) at room temperature yielded CS-6 NPs and CS-7 respectively. The structure of new chitosan derivatives was characterized using morphological and spectroscopic analyses. From evaluation of the biological activities, the greatest enzymatic inhibitory for trypsin and α-chymotrypsin revealed by CS-7 at 88.33 ± 2.27 and 79.63 ± 3.16% respectively. Furthermore, the highest inhibition zones, (MIC) and (MBC) against S. aureus and B. subtilis recorded by CS-6 NPs at 21 ± 0.75, 22 ± 0.98 mm, 19.5, 19.5, 38 and 38 ppm respectively. Additionally, CS-8 displayed the best cell growth inhibition against vero cell line at 93.17 ± 0.29%.

Sustainable antimicrobial modified chitosan and its nanoparticles hydrogels: Synthesis and characterization.

The target of the present study is the development of sustainable chitosan and chitosan nanoparticles-based heterocyclic compound hydrogels with antimicrobial properties. Sustainable antimicrobial new modified chitosan hydrogel (CS-3) was synthesized by the reaction of chitosan (CS) with 2-([4-[(1, 3-dioxoisoindolin-2-ylimino) methyl] phenyl] methyleneamino) isoindoline-1, 3-dione (3) via ring opening of cyclic imide moiety in compound (3). However, the modified chitosan nanoparticles hydrogel (CS-3 NPs) were prepared in-situ by an ionotropic gelation technique using sodium tripolyphosphate (TPP) as the cross-linking agent. The prepared hydrogels were characterized by FTIR, SEM, TEM, TGA, DSC and elemental analysis. The hydrogels were tested versus eight pathogenic strains of Gram +ve and Gram -ve bacteria and two fungi. The results revealed that hydrogels (CS-3) and (CS-3 NPs) showed higher antimicrobial activities than virgin (CS) and (CS-NPs). However, hydrogel (CS-3 NPs) showed the highest Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) especially with Gram +ve bacteria (S. pyogenes) at 19.5 and 39 µg/ml compared to the standard antibiotic Ciprofloxacin at 19 and 38 µg/ml respectively.

Novel hydrazinocurcumin derivative loaded chitosan, ZnO, and au nanoparticles formulations for drug release and cell cytotoxicity.

Synthesis of new hydrazinocurcumin derivative 4-((E)-2-(1-(4-Methoxy benzyl)-6-p-tolylpyridazin-3-yl)-3-((E)-4-hydroxy-3-methoxystyryl)-1H-pyrazol-5-yl)vinyl)-2-methoxyphenol (HCUR) through the reaction of curcumin (CUR) with 1- (4-(2-Methoxybenzyl)-6-p-tolylpyridazin-3-yl)hydrazine(VII). Nanoparticles formulations of (HCUR) loaded chitosan (CS), ZnO, Au, CS-ZnO and CS-Au NPs, via self-assembling process were developed to give CS-HCUR NPs, ZnO-HCUR NPs, Au-HCUR NPs, CS-ZnO-HCUR NPs and CS-Au-HCUR NPs. Chemical structures of (HCUR) and (HCUR) loaded nanoparticles formulations were characterized by UV-Vis, FTIR, Mass Spectrum, Elemental Analysis, 1HNMR, 13CNMR, TGA, DSC, SEM and TEM. The particle size of the nanoformulations ranged from 16.8 to 59.6 nm. NPs formulations were used as delivery system to sustain controlled drug delivery. Drug release profiles and cytotoxicity of NPs formulations against HCT-116 (colon carcinoma) and HepG-2 (hepatocellular cancer) cell lines were investigated. Drug release studies showed that by decreasing the pH value of release medium from 7.4 to 5.4 increased the release rate of (HCUR) from the NPs formulations. Cell viability study proved that NPs formulations revealed higher activity against HCT- 116 cell than (CUR) especially CS-HCUR NPs which displayed the most active with cell viability 1.80%. Moreover, ZnO-HCUR NPs expressed as the highest cytotoxic effect against HepG-2 cell with cell viability 0.98%.

Chitosan nanoparticle hydrogel based sebacoyl moiety with remarkable capability for metal ion removal from aqueous systems.

In this present study, a new modified chitosan hydrogel, Cts-SC NPs, was prepared from a one pot reaction of sebacoyl chloride (SC) with chitosan in the presence of 1% v/v glacial acetic acid and 1% w/v sodium tripolyphosphate (TPP) using an ionotropic gelation technique. The modified chitosan hydrogel, Cts-SC NPs, was characterized by FTIR, TEM, XRD, TGA, DSC and SEM. The adsorption efficiency of Cts-SC NPs for metal ions Hg2+, Ni2+ and Co2+ from aqueous solution was evaluated. The effects of various parameters such as contact time, pH and initial metal ions concentration were investigated. Adsorption isotherm data were fitted using different two-parameter models. Modified chitosan hydrogel Cts-SC NPs had remarkable adsorption of Hg2+, Ni2+ and Co2+ ions than chitosan hydrogel Cts-NPs. The antimicrobial activity of Cts-NPs towards the bacteria, Bacillus subtilis, Pseudomonas aeruginosa and fungus Aspergillus flavus was improved by modification with sebacoyl chloride to give Cts-SC NPs.

New heterocycle modified chitosan adsorbent for metal ions (II) removal from aqueous systems.

A new hydrogel based on a modified chitosan CS-B was synthesized and evaluated for its metal ion removal from aqueous systems. The CS-B hydrogel was prepared through modification of chitosan with 4-((1, 3-dioxoisoindolin-2-ylimino) methyl) benzaldehyde as a heterocyclic component. The new hydrogel was analyzed by diverse techniques such as FTIR, XRD, TGA, SEM, and swelling tests. The adsorption capacity of CS-B for metal ions Co(2+), Hg(2+), Cu(2+), Zn(2+), and Pb(2+) from aqueous systems at different pH values showed various levels of efficiency. The metal ion uptake data over a range of pH values for Co(2+) and Hg(2+) showed the highest adsorption capacity while Cu(2+), Zn(2+), and Pb(2+) showed moderate adsorption capacity. Selective metal ion efficiency was highest for Co(2+) and lowest for Hg(2+) in their binary mixture.