Search Results (23)

Biopolymer-based packaging films possess outstanding performances and are being developed as the alternatives to traditional petroleum-based plastic packaging films with many non-ignorable shortcomings. In this study, chitosan, succinylated pullulan (SP), and berberine (BBR) were combined to fabricate novel biopolymer-based composite films (CSSPB) via the layer-by-layer assembly method. The effects of the incorporation of BBR on the physicochemical properties of the film were investigated. It was found that after BBR was added, the tensile strength (TS), elongation at break (EAB), hydrophobicity, and antioxidant capacities of the film were enhanced. The chemical bonding, crystalline properties, elemental composition, and thermal stability of the films were also characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA), respectively. The in vitro antifungal tests revealed the antifungal activities of the films with a relatively high BBR content against Colletotrichum gloeosporioides (CG). In the preservation experiments, the CSSPB films exhibited preservation effects on fresh-cut apples, which manifested as delaying browning, weight loss, an increase in the soluble solids content, and a decrease in hardness. The new CSSPB composite films were opined to hold application potential in the field of food packaging. Full article

Developing a rapidly gel-forming, in situ sprayable hydrogel with wound dressing functionality is essential for enhancing the wound healing process. In this study, a novel sprayable hydrogel-based wound dressing was developed by combining thermo- and pH- responsive polymers including Pluronic F127 (PF127) and N-succinyl chitosan (NSC). NSC was prepared by modifying chitosan with succinic anhydride, as confirmed by Fourier-transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The NSC synthesized using a succinic anhydride-to-chitosan molar ratio of 5:1 exhibited the highest degree of substitution, resulting in a water-soluble polymer effective over a broad pH range. The formulation process of the PF127:NSC sprayable hydrogel was optimized and evaluated based on its sol–gel phase transition behavior, clarity, gelation time, liquid and moisture management, stability, and cytotoxicity. These properties can be suitably tailored by adjusting the concentrations of PF127 and NSC. Moreover, the antioxidant capacity of the hydrogels was enhanced by incorporating Azadirachta indica (neem) extract, a bioactive compound, into the optimized sprayable hydrogel. Both neem release and antioxidant activity increased in a dose-dependent manner. Overall, the developed sprayable hydrogel exhibited favorable sprayability, appropriate gelation properties, controlled drug release, and antioxidant activity, underscoring its promising translational potential as a wound dressing. Full article

The formation of self-crosslinking chitosan hydrogels using carboxylic acids has a number of limitations. Chitosan dissolves in oxalic, malonic, and succinic acids at a ratio of 1 amino group to 2 carboxyl groups into viscous solutions (G′ < G′′), but does not dissolve with lower amounts of the acid. Mixing chitosan hydrochloride with disodium carboxylates does not afford gels, but only a coacervate in the case of disodium oxalate, which dissolves upon dialysis. In the homologous series of N-carboxyalkyl derivatives (alkyl = methyl, ethyl, propyl), all members form gels (G′ > G′′). At approx. 50% of substitution, the storage modulus increases from 40 Pa (methyl) to 30,000 Pa (propyl) indicating the increasing strength of intermolecular interactions with the increasing length of the alkyl spacer. This could indicate that a sufficiently long spacer is required to properly connect the chitosan helices. N-succinyl chitosan, where the spacer is attached to the backbone as an amide, also forms polymer gels across all degrees of N-acylation. When compared to N-carboxypropyl chitosan, the latter forms significantly stiffer gels that swell less. This indicates that one covalent bond, a sufficient length, and the conformational flexibility of the spacer are important for gelation. Full article

Background: In tissue engineering, developing injectable hydrogels with tailored mechanical and bioactive properties remains a challenge. This study introduces an injectable hydrogel composite for soft tissue regeneration, composed of oxidized alginate (OA) and N-succinyl chitosan (NSC) cross-linked via Schiff base reaction, reinforced with graphene oxide (GOx) and cyclic arginylglycylaspartic acid (c-RGD). The objective was to create a multifunctional platform combining injectability, bioactivity, and structural stability. Methods: The OA/NSC/GOx-cRGD hydrogel was synthesized through Schiff base cross-linking (aldehyde-amine reaction). Characterization included FTIR (C=N bond at 1650 cm⁻¹), Raman spectroscopy (D/G bands at 1338/1567 cm⁻¹), SEM (porous microstructure), and rheological analysis (shear-thinning behavior). In vitro assays assessed fibroblast viability (MTT) and macrophage TNF-α secretion (ELISA), while ex-vivo injectability and retention were evaluated using chicken cardiac tissue. Results: The hydrogel exhibited shear-thinning behavior (viscosity: 10 to <1 Pa·s) and elastic-dominated mechanics (G′ > G″), ensuring injectability. SEM revealed an interconnected porous structure mimicking native extracellular matrix. Fibroblast viability remained ≥95%, and TNF-α secretion in macrophages decreased by 80% (30 vs. 150 pg/μL in controls), demonstrating biocompatibility and anti-inflammatory effects. The hydrogel adhered stably to cardiac tissue without leakage. Conclusions: The OA/NSC/GOx-cRGD composite integrates injectability, bioactivity, and structural stability, offering a promising scaffold for tissue regeneration. Its modular design allows further functionalization with peptides or growth factors. Future work will focus on translational applications, including scalability and optimization for dynamic biological environments. Full article

Anti-cancer targeted therapy is a promising approach. However, the identification of target molecules over-expressed in a wide range of tumors remains a significant challenge. The aim of this study was to analyze the expression of cell membrane-exposed heat shock protein 70 kDa (mHSP70) on different tumor cells and to develop a nanoscale delivery system based on a monoclonal antibody (mAb) that recognizes mHSP70 and uses chitosan core–shell nanoparticles (NPs). Several types of tumor cells (breast, pancreas, colon, prostate cancers, and some lymphomas) expressed mHSP70 as was determined by flow cytometry and confocal microscopy both in 2D and 3D cultures. Core NPs were formed by chitosan (C) conjugated to allocolchicinoid, which was used as a model drug (D). mAbs (A) targeting mHSP70 were complexed with succinylchitosan and used as NP shells forming final CAD-NPs. These NPs were characterized by size, charge, and functional activity. CAD-NPs were shown to have additional toxicity in comparison with CD-NPs in mHSP7-positive cells. Taken collectively, this study shows that mAb to mHSP70 can be used as a targeting vector in antitumor therapy. Full article

Background: The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Methods: Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. Results: For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Conclusions: Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi’s protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract. Full article

Chitosan (CS) is a polysaccharide obtainable by the deacetylation of chitin, which is highly available in nature and is consequently low-cost. Chitosan is already used in the biomedical field (e.g., guides for nerve reconstruction) and has been proposed as a biomaterial for tissue regeneration in different body districts, including bone tissue. The interest in chitosan as a biomaterial stems from its ease of functionalization due to the presence of reactive groups, its antibacterial properties, its ease of processing to obtain porous matrices, and its inherent similarity to polysaccharides that constitute the human extracellular matrix, such as hyaluronic acid (HA). Here, chitosan was made to react with succinic anhydride to develop a negatively charged chitosan (SCS) that better mimics HA. FT-IR and NMR analyses confirmed the presence of the carboxylic groups in the modified polymer. Four different electrospun matrices were prepared: CS, SCS, a layer-by-layer matrix (LBL), and a matrix with both CS and SCS simultaneously electrospun (HYB). All the matrices containing SCS showed increased human osteoblast proliferation, mineralization, and gene expression, with the best results obtained with HYB compared to the control (CS). Moreover, the antibacterial potential of CS was preserved in all the SCS-containing matrices, and the pure SCS matrix demonstrated a significant reduction in bacterial proliferation of both S. aureus and E. coli. Full article

The synthesis of octenyl-succinylated chitosan with different degrees of substitution resulting from chemical modification of chitosan and controlled addition of octenyl succinic acid was investigated. The modified products were characterized using ¹H NMR, FTIR, and XRD, and the degree of substitution was also determined. The properties of the modified chitosan oligosaccharide in solution were evaluated by surface tension and dye solubilization, finding that the molecules self-assembled when they are above the critical aggregation concentration. The two methods yielded consistent results, showing that the self-assembly was reduced with higher levels of substitution. The antimicrobial activity of the octanyl-succinylated chitosan oligosaccharide (OSA-COS) derivatives against Staphylococcus aureus, Escherichia coli, and Fusarium oxysporum f.sp cucumerinum was investigated by the Oxford cup method. While the acetylated COS derivatives were not significantly effective against either E coli or S. aureus, they showed significant antifungal activity toward F. oxysporum that was superior to that of COS. The modified product was found to form a stable emulsion when mixed with whey protein isolate. The emulsion formed by the highly substituted derivatives have a certain stability and loading efficiency, which can be used for the encapsulation and delivery of astaxanthin. Full article

IgE-mediated allergic reaction occurs in response to harmless environmental compounds, such as tree and grass pollen, fragments of household microorganisms, etc. To date, the only way to treat IgE-mediated allergy is allergen-specific immunotherapy (ASIT), which consists of a prolonged subcutaneous administration of allergen extracts or recombinant proteins. The long duration of the treatment, the cost and the risk of life-threatening adverse reactions are the main limiting factors for ASIT. The aim of this work was to develop allergen proteins encapsulated in chitosan-based microparticles that can be safely administered at high doses and in a rash protocol. The egg white allergen, Gal d 1 protein, was used as a model antigen. The protein was packed into core–shell type microparticles (MPs), in which the core was formed with succinyl chitosan conjugated to Gal d 1, subsequently coated with a shell formed by quaternized chitosan. The obtained core–shell MPs containing Gal d 1 in the core (Gal-MPs) were non-toxic to macrophage and fibroblast cell lines. At the same time, Gal-MPs were quickly engulfed by bone marrow-derived dendritic cells or RAW264.7 macrophage cells, as was visualized using flow cytometry and confocal microscopy. Encapsulated Gal d 1 was not recognized by Gal d 1-specific IgE in ELISA. Female BALB/c mice were immunized with Gal-MPs subcutaneously three times a week for 2 weeks. Immunization of mice resulted in IgG titers 1250 ± 200 without IgE production. Allergy in control and vaccinated mice was induced by low-dose Gal d 1 injections in the withers of mice. IgE was induced in control-sensitized but not in the vaccinated mice. Thus, preventive vaccination with the encapsulated allergens is safe and rapid; it significantly reduces the risk of IgE production induced by respiratory and oral allergens. Full article

This work aimed at preparing nanomicelles from N-benzyl-N,O-succinyl chitosan (NBSCh) loaded with a curcumin analog, 2,6-bis((3-methoxy-4-hydroxyphenyl) methylene) cyclohexanone, a.k.a. cyqualone (CL), for antineoplastic colon cancer chemotherapy. The CL-loaded NBSCh micelles were spherical and less than 100 nm in size. The entrapment efficiency of CL in the micelles ranged from 13 to 39%. Drug release from pristine CL was less than 20% in PBS at pH 7.4, whereas the release from CL-NBSCh micelles was significantly higher. The release study of CL-NBSCh revealed that around 40% of CL content was released in simulated gastric fluid at pH 1.2; 79 and 85% in simulated intestinal fluids at pH 5.5 and 6.8, respectively; and 75% in simulated colonic fluid at pH 7.4. CL-NBSCh showed considerably high selective cytotoxicity towards mucosal epithelial human colon cancer (HT-29) cells and lower levels of toxicity towards mouse connective tissue fibroblasts (L929). CL-NBSCh was also more cytotoxic than the free CL. Furthermore, compared to free CL, CL-NBSCh micelles were found to be more efficient at arresting cell growth at the G2/M phase, and induced apoptosis earlier in HT-29 cells. Collectively, these results indicate the high prospective potential of CL-loaded NBSCh micelles as an oral therapeutic intervention for colon cancer. Full article

The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3–8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130–318 μg/mg. The size of the obtained particles was 100–200 nm, and the ζ-potential varied from −22 to −28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1–0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20–60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics. Full article

To avoid fungal spreading in the bloodstream and internal organs, many research efforts concentrate on finding appropriate candidiasis treatment from the initial stage. This paper proposes chitosan-based physically or chemically cross-linked hydrogels aimed to provide sustained release of micronized nystatin (NYSm) antifungal drug, known for its large activity spectrum. Nystatin was demonstrated itself to provide hydrodynamic/mechanic stability to the chitosan hydrogel through hydrophobic interactions and H-bonds. For chemical cross-linking of the succinylated chitosan, a non-toxic diepoxy-functionalized siloxane compound was used. The chemical structure and composition of the hydrogels, also their morphology, were evidenced by infrared spectroscopy (FTIR), by energy dispersive X-ray (EDX) analysis and by scanning electron microscopy (SEM), respectively. The hydrogels presented mechanical properties which mimic those of the soft tissues (elastic moduli < 1 MPa), necessary to ensure matrix accommodation and bioadhesion. Maximum swelling capacities were reached by the hydrogels with higher succinic anhydride content at both pH 7.4 (429%) and pH 4.2 (471%), while higher amounts of nystatin released in the simulative immersion media (57% in acidic pH and 51% in pH 7.4) occurred from the physical cross-linked hydrogel. The release mechanism by non-swellable matrix diffusion and the susceptibility of three Candida strains make all the hydrogel formulations effective for NYSm local delivery and for combating fungal infections. Full article

In situ-forming, biodegradable, and self-healing hydrogels, which maintain their integrity after damage, owing to dynamic interactions, are essential biomaterials for bioapplications, such as tissue engineering and drug delivery. This work aims to develop in situ, biodegradable and self-healable hydrogels based on dynamic covalent bonds between N-succinyl chitosan (S-CHI) and oxidized aldehyde hyaluronic acid (A-HA). A robust effect of the molar ratio of both S-CHI and A-HA was observed on the swelling, mechanical stability, rheological properties and biodegradation kinetics of these hydrogels, being the stoichiometric ratio that which leads to the lowest swelling factor (×12), highest compression modulus (1.1·10⁻³ MPa), and slowest degradation (9 days). Besides, a rapid (3 s) self-repairing ability was demonstrated in the macro scale as well as by rheology and mechanical tests. Finally, the potential of these biomaterials was evidenced by cytotoxicity essay (>85%). Full article

Due to the limitation in the current treatment modalities, such as secondary surgery in ACI and fibrocartilage formation in microfracture surgery, various scaffolds or hydrogels have been developed for cartilage regeneration. In the present study, we used sodium periodate to oxidize methylcellulose and formed dialdehyde methylcellulose (DAC) after dialysis and freeze-drying process, DAC was further mixed with succinyl-chitosan (SUC) to form an DAC-SUC in situ forming hydrogel. The hydrogel is a stiffness, elastic-like and porous hydrogel according to the observation of SEM and rheological analysis. DAC-SUC13 hydrogel possess well cell-compatibility as well as biodegradability. Most bone marrow mesenchymal stem cells (BM-pMSCs) were alive in the hydrogel and possess chondrogenesis potential. According to the results of animal study, we found DAC-SUC13 hydrogel can function as a stem cell carrier to promote glycosaminoglycans and type II collagen synthesis in the osteochondral defects of porcine knee. These findings suggested that DAC-SUC13 hydrogel combined with stem cell is a potential treatment for cartilage defects repair in the future. Full article

Curcumin-loaded native and succinylated pea protein nanoparticles, as well as zwitterionic giant unilamellar vesicles were used in this study as model bioactive compound loaded-nanoparticles and biomembranes, respectively, to assess bio-nano interactions. Curcumin-loaded native protein-chitosan and succinylated protein-chitosan complexes, as well as native protein-chitosan and succinylated protein-chitosan hollow, induced leakage of the calcein encapsulated in the giant unilamellar vesicles. The leakage was more pronounced with hollow protein-chitosan complexes. However, curcumin-loaded native protein and curcumin-loaded succinylated protein nanoparticles induced calcein fluorescence quenching. Dynamic light scattering measurements showed that the interaction of curcumin-loaded native protein, curcumin-loaded succinylated protein, native protein-chitosan, and succinylated protein-chitosan complexes with the giant unilamellar vesicles caused a major reduction in the size of the lipid vesicles. Confocal and widefield fluorescence microscopy showed rupturing of the unilamellar vesicles after treatment with native pea protein-chitosan and succinylated pea protein-chitosan complexes. The nature of interaction between the curcumin-loaded protein nanoparticles and the biomembranes, at the bio-nano interface, is influenced by the encapsulated curcumin. Findings from this study showed that, as the protein plays a crucial role in stabilizing the bioactive compound from chemical and photodegradation, the encapsulated nutraceutical stabilizes the protein nanoparticle to reduce its interaction with biomembranes. Full article