Chitosan Conjugates Research Articles

Fabrication of curcumin-loaded nano-micelles based on quercetin-quarternary ammonium-chitosan (Qu-QCS) conjugate and evaluation of synergistic effect with doxorubicin against breast cancer

The applications of quarternized chitosans have achieved notable success in the development of drug-delivery systems. This study reported the preparation of quercetin-quarternized chitosan (Qu-QCS) conjugate and its application for the fabrication of stable and safe curcumin (cur) loaded nano-micelles with high targeting ability and selectivity towards the breast cancer cell lines. Moreover, doxorubicin (dox) was co-treated with the nanomicelles to enhance the efficacy and reduce the cardiotoxic effects of dox. Structural properties of Qu-QCS were evaluated by FTIR, DSC, and XRD analysis and the yield obtained was 48.82 %. The nano-micelles obtained showed spherical shape, <200 nm size, 48.38 % entrapment efficiency, prolonged stability at 4 °C and pH-responsive release pattern. The cur-loaded nano-micelles showed higher activity and selectivity against breast cancer (MCF-7 and MDA-MB-231) cell lines with enhanced internalization, lower toxicity to the normal cardiomyoctyes (H9C2), enhanced the cell cycle arrest at the G2/M phase of the breast cancer cell lines and induced apoptosis with high intensity compared to pure cur. Moreover, the co-treatment of dox with cur-loaded Qu-QCS nano-micelles showed increased anticancer activity and reduced cardiotoxicity. Overall, this study suggests the potential applications of cur-loaded Qu-QCS micelles in the delivery of chemotherapeutic agents and complementary support in combination with chemotherapeutic agents.

Exploring the promising role of chitosan delivery systems in breast cancer treatment: A comprehensive review

Breast cancer presents a significant global health challenge, driving the development of novel treatment strategies for therapeutic interventions. Nanotechnology has emerged as a promising avenue for addressing this challenge, with Chitosan (CS) nanoparticles receiving prominence due to their unique characteristics and multitude of potential applications. This review provides a comprehensive overview of the role of Chitosan nanoparticles in breast cancer therapy. The review begins by emphasizing the prevalence and importance of breast cancer as a major health issue, underscoring the necessity for effective treatments. It then delves into the application of Chitosan nanoparticles in breast cancer therapy. One key aspect discussed is their role as carriers for anticancer drugs, enabling targeted delivery and improved cellular uptake. Furthermore, the review explores modified Chitosan nanoparticles and strategies for enhancing their efficacy and specificity in breast cancer treatment. It also examines Chitosan conjugates and hybrids, which offer innovative approaches for combination therapy. Additionally, metal and magnetic Chitosan nanoparticles are discussed spanning their capacity to assist in imaging, hyperthermia, as well as targeted drug delivery. In conclusion, the review summarizes the current research landscape regarding Chitosan nanoparticles for breast cancer therapy and offers insights into future directions. Overall, the review highlights the versatility, potential benefits, and future prospects of Chitosan nanoparticles in combating breast cancer.

Conjugation of CRAMP18-35 Peptide to Chitosan and Hydroxypropyl Chitosan via Copper-Catalyzed Azide-Alkyne Cycloaddition and Investigation of Antibacterial Activity.

We developed a synthesis strategy involving a diazo transfer reaction and subsequent click reaction to conjugate a murine cathelicidin-related antimicrobial peptide (CRAMP18-35) to chitosan and hydroxypropyl chitosan (HPC), confirmed the structure, and investigated the antimicrobial activity. Chitosan azide and HPC-azide were prepared with a low degree of azidation by reacting the parent chitosan and HPC with imidazole sulfonyl azide hydrochloride. CRAMP18-35 carrying an N-terminal pentynoyl group was successfully grafted onto chitosan and HPC via copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The chitosan-peptide conjugates were characterized by IR spectroscopy and proton NMR to confirm the conversion of the azide to 1,2,3-triazole and to determine the degree of substitution (DS). The DS of the chitosan and HPC CRAMP18-35 conjugates was 0.20 and 0.13, respectively. The antibacterial activity of chitosan-peptide conjugates was evaluated for activity against two species of Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), and two species of Gram-negative bacteria, Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The antimicrobial peptide conjugates were selectively active against the Gram-negative bacteria and lacking activity against Gram-positive bacteria.

Effect of chitosan conjugates with oxycinnamic acids and &lt;i&gt;Bacillus subtilis&lt;/i&gt; bacteria on the activity of protective proteins and resistance of potato plants to &lt;i&gt;Phytophthora infestans&lt;/i&gt;

The effect of chitosan conjugates with caffeic (ChCA) and ferulic (ChFA) acids in combination with Bacillus subtilis bacteria on the transcriptional activity of PR protein genes and proteome changes in potato plants during infection with Phytophthora infestans (Mont.) de Bary was studied. Plants grown from mini tubers of the Luck variety were sprayed with solutions of ChCA and ChFA, suspension of B. subtilis bacteria strains 26D and 11 VM, composites of ChCA of ChFA together with bacteria. 3 days after treatment, some of the plants were infected with P. infestans. A decrease in the degree of development of the pathogen of late blight on potato leaves in all treatment options was revealed. The maximum protective effect was manifested when plants were treated with bacteria B. subtilis strain 26D in combination with conjugates of chitosan and oxycinnamic acids. The mechanisms of increasing the resistance of potato plants to P. infestans were associated with the activation of transcriptional activity of genes encoding the main protective protein (PR‑1), chitinase (PR‑3), thaumatin-like protein (PR‑5), protease inhibitor (PR‑6), peroxidase (PR‑9), ribonuclease (PR‑10). The revealed activation of the expression of marker genes of systemic acquired resistance and induced systemic resistance under the influence of joint treatment of plants with B. subtilis and chitin conjugates with oxycinnamic acids indicate the synergistic development of protective reactions in potato plants in this variant. By the method of two-dimensional electrophoresis of S. tuberosum leaf proteins followed by MALDI-TOF analysis, 12 proteins were identified, the presence of which in the leaves differed depending on the variant of the experiment. In all treatment variants, suppression of serine-threonine protein phosphatase activity was observed, reflecting the development of the hypersensitivity reaction. Different variants of the experiment formed weakly expressed clusters, which indicates multiple mechanisms of regulation of the synthesis of protective proteins involved in the reaction to treatment with bacteria, chitosan conjugates and infection with P. infestans.

The Influence of Chitosan Derivatives in Combination with Bacillus subtilis Bacteria on the Development of Systemic Resistance in Potato Plants with Viral Infection and Drought.

Viral diseases of potatoes are among the main problems causing deterioration in the quality of tubers and loss of yield. The growth and development of potato plants largely depend on soil moisture. Prevention strategies require comprehensive protection against pathogens and abiotic stresses, including modeling the beneficial microbiome of agroecosystems combining microorganisms and immunostimulants. Chitosan and its derivatives have great potential for use in agricultural engineering due to their ability to induce plant immune responses. The effect of chitosan conjugate with caffeic acid (ChCA) in combination with Bacillus subtilis 47 on the transcriptional activity of PR protein genes and changes in the proteome of potato plants during potato virus Y (PVY) infection and drought was studied. The mechanisms of increasing the resistance of potato plants to PVY and lack of moisture are associated with the activation of transcription of genes encoding PR proteins: the main protective protein (PR-1), chitinase (PR-3), thaumatin-like protein (PR-5), protease inhibitor (PR-6), peroxidase (PR-9), and ribonuclease (PR-10), as well as qualitative and quantitative changes in the plant proteome. The revealed activation of the expression of marker genes of systemic acquired resistance and induced systemic resistance under the influence of combined treatment with B. subtilis and chitosan conjugate indicate that, in potato plants, the formation of resistance to viral infection in drought conditions proceeds synergistically. By two-dimensional electrophoresis of S. tuberosum leaf proteins followed by MALDI-TOF analysis, 10 proteins were identified, the content and composition of which differed depending on the experiment variant. In infected plants treated with ChCA, the synthesis of proteinaceous RNase P 1 and oxygen-evolving enhancer protein 2 was enhanced in conditions of normal humidity, and 20 kDa chaperonin and TMV resistance protein N-like was enhanced in conditions of lack of moisture. The virus coat proteins were detected, which intensively accumulated in the leaves of plants infected with potato Y-virus. ChCA treatment reduced the content of these proteins in the leaves, and in plants treated with ChCA in combination with Bacillus subtilis, viral proteins were not detected at all, both in conditions of normal humidity and lack of moisture, which suggests the promising use of chitosan derivatives in combination with B. subtilis bacteria in the regulation of plant resistance.

Insight into enhancing the performance of sludge dewatering using a novel flocculant CS–TA prepared through free radical-mediated conjugation

ABSTRACT Flocculation is one of the most significant conditioning methods for sludge dewatering. In the study, a novel flocculant CS–TA, prepared through free radical-mediated conjugation of tannic acid (TA) and chitosan (CS), was proposed to improve sludge dewatering. The characterisation using Fourier transform infra-red spectroscopy and X-ray diffraction analysis shows that the CS chain was the backbone of CS–TA, and the presence of CS–TA aromatic rings confirmed the conjugation of CS with TA. Moreover, the conditioning of CS–TA yielded the best dewatering performance at 30 mg g TS−1 with the water content of sludge cake by press filtration (Wsc) of 59.78% ± 0.3% and capillary suction time (CST) of 11.8s ± 0.35 s, compared to 98.2% ± 0.15% and 56.2 s ± 0.16 in raw sludge. The results of different influencing factors (e.g. pH and temperature) on flocculation efficiency indicated that CS–TA possessed the capacity for enhancing sludge dewaterability over a wide range of pH, and the optimal temperature was observed to be 35 °C. Furthermore, the increase of particle size and zeta potential implied the addition of CS–TA favoured the formation of larger particles charge neutralisation and adsorption bridging effect. In addition, extracellular polymer substances (EPS) analysis indicated that the decrease in the polysaccharide and protein contents in EPS after CS–TA addition could increase the relative hydrophobicity of sludge. Moreover, the contents of heavy metals in sludge and their leaching toxicity and environmental risk were reduced. This study provides comprehensive insights into the exploration of CS–TA for sludge dewatering and the maintenance of ecological security in an eco-friendly.

RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CURCUMIN AND RESVERATROL IN NANO-MICELLE: DUAL DRUG DUAL FORM SIMULTANEOUS ESTIMATION

Objective: To develop a reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous estimation of conjugated form of Curcumin (CCMN) and free form of Resveratrol (RSV) in nano-micelle. Methods: The conjugation of lipophilic CCMN and hydrophilic Chitosan (CHT) through succinyl linker produce amphipathic molecule that can self-assemble into RSV solution to form micelle. Here RSV exists in micelle core as free form and CCMN with micelle backbone as conjugated form. So it required to estimate conjugated drug and free drug simultaneously from nano-micelle. We developed a RP-HPLC method, utilized C18 column, follow flow rate of mobile phase 1.0 ml/min, which consist of acetonitrile with water (0.5% Ortho Phosphoric acid, pH 4.6) in the ratio of 1:1 for 20 min. Injection volume was 10μl and column temperature 25 ℃. Isosbestic detection of both drugs was at 254 nm. Results: The retention time of RSV and CCMN were at 8.15 min and 11.41 min respectively, completely distinguished sharp peak of CCMN and RSV developed with resolution 7.360±0.117, wide range of linearity with correlation coefficient value (R2) of CCMN and RSV were 0.99987 and 0.99992 respectively and recovery value of CCMN and RSV were 100.041±0.22 % and 100.041±0.21 % respectively. The RSD (relative standard deviation) for accuracy, precision and robustness of the method was found to be less than 2%. Conclusion: The develop method for simultaneous estimation of conjugated CCMN and free form of RSV in the nano-micelle formulation was consider to be accurate, precise, robust and sensitive.

Low molecular weight chitosan based GSH-responsive self-assembled cationic micelle with enhanced anti-tumor effect by combining oxidative damage and chemotherapy

A novel cationic lipoic acid grafted low molecular weight chitosan (LCNE-LA) conjugate was constructed and further self-assembled into GSH-responsive cationic nanocarrier to achieve better antitumor effect by combining encapsulated chemotherapy and oxidative damage induced by ROS. The resultant LCNE-LA cationic micelle exhibited favorable physicochemical properties (low CMC, small size, positively zeta potential and good stability), excellent biosafety and desired redox sensitivity. Next, doxorubicin (Dox) was embedded into hydrophobic core to form stable Dox/LCNE-LA micelle that had superior loading capacity. The GSH-induced release behavior, cellular uptake ability, ROS generation and GSH consumption capacity and in vitro antitumor activity of Dox/LCNE-LA micelle were systematically evaluated. Consequently, Dox/LCNE-LA cationic micelle with positively charged could efficiently enter into cancer cell and redox-sensitive release Dox via disulfide-thiol exchange reaction, which usually expend abundant GSH and disrupt redox homeostasis. Studies further confirmed that Dox/LCNE-LA micelle could increase ROS and reduced GSH content which might cause oxidative damage to tumor cell. Antitumor activity indicated that Dox/LCNE-LA micelle achieved an excellent cancer-killing effect, which might be attributed to combination treatment of Dox and ROS induce oxidative damage. Overall, this research was expected to provide a platform for antitumor treatment by triggering Dox release and promoting ROS generation.

The Effect of Chitosan Conjugates with Hydroxycinnamic Acids and Bacillus subtilis Bacteria on the Activity of Protective Proteins and Resistance of Potato Plants to Phytophthora infestans

The Effect of Chitosan Conjugates with Hydroxycinnamic Acids and Bacillus subtilis Bacteria on the Activity of Protective Proteins and Resistance of Potato Plants to Phytophthora infestans

Antimicrobial fibres derived from aryl-diazonium conjugation of chitosan with Harakeke (Phormium tenax) and Hemp (Cannabis sativa) Hurd

Surface functionalisation of natural materials to develop sustainable and environmentally friendly antimicrobial fibres has received great research interest in recent years. Herein, chitosan covalent conjugation via aryl-diazonium based chemistry onto Phormium tenax fibres (PTF) and hemp hurds (HH) was investigated. PTF are fibres derived from Harakeke/New Zealand flax, an indigenous and abundant plant source of leaf fibres, which served as an important 19th century export commodity of New Zealand. HH are obtained as a by-product from the hemp (Cannabis sativa) industry and find applications as traditional construction material, animal bedding, chemical absorbent, insulation, fireboard etc. This study reports aryl-diazonium covalent attachment of chitosan and PD13 (6-O-(3-(2-(N,N-dimethylamino)ethylamino)-2-hydroxypropyl)chitosan), a chitosan derivative with improved antibacterial activity, on to PTF and HH. The modification was confirmed using FTIR, XPS, SEM and water contact angle studies. Comparison of aryl-diazonium versus the use of succinic anhydride bridging for chitosan attachment was also investigated, with the diazonium method giving improved results. The treated PTF and HH fibres had good antibacterial activity against Staphylococcus aureus and this study contributes to the development of sustainable antibacterial fibres using bio-based materials.

Efficacy of a Maillard-type conjugate of whey protein isolate with chitosan as a carrier for a liposomal form of a combination of curcumin and balanced amounts of n-3 and n-6 PUFAs. Part I. structure – Functionality relationships

The Maillard-type WPI–chitosan conjugate was prepared through dry heating at 60 °C and 75% relative humidity for 72 h at a weight excess of WPI (8.7-fold) relative to CHIT (75% of deacetylation). The focus of the study was the soluble fraction (68% w/w) of the WPI–CHIT conjugate in the pI range of WPI (pH 4.5). SDS-PAGE analysis revealed that 16% of the total WPI was covalently bonded to CHIT. SDS-PAGE and SEC identified a 29% degree of binding for α-lactalbumin. DSC, fluorimetry, and FTIR detected unfolding of globular whey proteins in the conjugate. The conjugate encapsulated 94% of phosphatidylcholine liposomes loaded with fish oil and curcumin, resulting in complex particles. EPRS, DSC, fluorimetry, laser light scattering, tensiometry, and TEM provided insights into the structural and thermodynamic parameters underlying the functionality of the latter: water solubility, protective ability for encapsulated nutraceuticals, and lower foaming ability compared to that of the WPI–CHIT conjugate.

Exploring biomedical applications of phenylboronic acid— functionalized chitosan conjugates

Exploring biomedical applications of phenylboronic acid— functionalized chitosan conjugates

Effect of Hydrophobic Chain Length in Amphiphilic Chitosan Conjugates on Intracellular Drug Delivery and Smart Drug Release of Redox-Responsive Micelle.

Three redox-sensitive nanocarriers were rationally designed based on amphiphilic low molecular weight chitosan-cystamine-octylamine/dodecylamin/cetylamine (LC-Cys-OA, LC-Cys-DA, LC-Cys-CA) conjugates containing disulfide linkage for maximizing therapeutic effect by regulating hydrophobic interaction. The resultant spherical micelles had the characteristics of low CMC, suitable size, excellent biosafety and desired stability. The drug-loaded micelles were fabricated by embedding doxorubicin (Dox) into the hydrophobic cores. The effect of hydrophobic chain lengths of amphiphilic conjugates on encapsulation capacity, redox sensitivity, trigger-release behavior, cellular uptake efficacy, antitumor effect and antimigratory activity of Dox-loaded micelles was systematically investigated. Studies found that Dox-loaded LC-Cys-CA micelle had superior loading capacity and enhanced redox sensitivity compared with the other two micelles. Release assay indicated that the three Dox-loaded micelles maintained sufficiently stability in normal blood circulation but rapidly disintegrated in tumor cells. More importantly, the LC-Cys-CA micelle with a longer hydrophobic chain length exhibited a higher accumulative Dox release percentage than the other two micelles. Additionally, an increase in hydrophobic chain lengths of amphiphilic conjugates improved cellular uptake efficiency, antitumor effect and antimigration activity of Dox-loaded micelles, which could be explained by enhanced loading ability and redox sensitivity. Our research was expected to provide a viable platform for achieving a desired therapeutic efficacy via the alteration of hydrophobic interaction.

Multi-crosslinked hydrogel built with hyaluronic acid-tyramine, thiolated glycol chitosan and copper-doped bioglass nanoparticles for expediting wound healing

The migration of fibroblasts and endothelial cells is a critical determinant of wound-healing outcomes for skin injuries. Here, hyaluronic acid-tyramine (HAT) and thiolated glycol chitosan (TGC) conjugates were combined with copper-doped bioglass (ACuBG) nanoparticles to build a novel type of multi-crosslinked hydrogel for stimulating the migration of cells, and thus, expediting wound healing. The optimally devised HAT/TGC/ACuBG gels had markedly improved strength and stiffness compared to the gels built from either HAT or TGC while showing sufficient elasticity, which contributes to stimulating the migration of fibroblasts. The sustainable release of silicon and copper ions from the gels was found to jointly induce the migration of human umbilical vein endothelial cells. The results based on mouse full-thickness skin defects demonstrated that they were able to fully restore the skin defects with formation of complete appendages within two weeks, suggesting their promising potency for use in expediting wound healing.

Kinetics, Equilibrium, and Thermodynamics for Conjugation of Chitosan with Insulin-Mimetic [meso-Tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadate(IV)(4-) in an Aqueous Solution.

This study investigated the conjugation of chitosan with the insulin-mimetic [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadate(IV)(4-), VO(tpps), in an aqueous medium as a function of conjugation time, VO(tpps) concentrations, and temperatures. To validate the synthesis of chitosan-VO(tpps) conjugate, UV-visible and Fourier transform infrared spectrophotometric techniques were utilized. Conjugate formation is ascribed to the electrostatic interaction between the NH3+ units of chitosan and the SO3- units of VO(tpps). Chitosan enhances the stability of VO(tpps) in an aqueous medium (pH 2.5). VO(tpps) conjugation with chitosan was best explained by pseudo-second-order kinetic and Langmuir isotherm models based on kinetic and isotherm studies. The Langmuir equation determined that the maximal ability of VO(tpps) conjugated with each gram of chitosan was 39.22 μmol at a solution temperature of 45 °C. Activation energy and thermodynamic studies (Ea: 8.78 kJ/mol, ΔG: -24.52 to -27.55 kJ/mol, ΔS: 204.22 J/(mol K), and ΔH: 37.30 kJ/mol) reveal that conjugation is endothermic and physical in nature. The discharge of VO(tpps) from conjugate was analyzed in freshly prepared 0.1 mol/L phosphate buffer (pH 7.4) at 37 °C. The release of VO(tpps) from the conjugate is a two-phase process best explained by the Higuchi model, according to a kinetic analysis of the release data. Taking into consideration all experimental findings, it is proposed that chitosan can be used to formulate both solid and liquid insulin-mimetic chitosan-VO(tpps) conjugates.

Conversion of liquid chitosan-based nanoemulsions into inhalable solid microparticles: Process challenges with polysaccharide

Solid particles ≤5 μm are essential to allow lower lung deposition and macrophage phagocytosis of anti-tubercular drugs. Decorating liquid nanoemulsion of anti-tubercular drug with macrophage-specific chitosan and chitosan-folate conjugate and spray drying the nanoemulsion with lactose produced oversized solid particles due to polysaccharide binding effects. This study designed solid nanoemulsion using lactose as the primary solid carrier and explored additives and spray-drying variables to reduce the binding and particle growth effects of chitosan. Deposition of magnesium stearate on lactose negated chitosan-inducible excessive lactose-liquid nanoemulsion binding and solid particle growth. Moderating the adhesion of chitosan-decorated liquid nanoemulsion onto lactose produced smooth-surface solid microparticles (size: 5.45 ± 0.26 μm; roughness: ∼80 nm) with heterogeneous size (span: 1.87 ± 1.21) through plasticization of constituent materials of nanoemulsion and lactose involving OH/N-H, C-H, CONH and/or COO moieties. Smaller solid particles could attach onto the larger particles with minimal steric hindrance by smooth surfaces. Together with round solid particulate structures (circularity: 0.919 ± 0.002), good pulmonary inhalation beneficial for treatment of pulmonary tuberculosis as well as other diseases is conferred.

Functionalized chitosan based nanotherapeutics to combat emerging antimicrobial resistance in bacterial pathogen

Ineffectiveness of conventional antibiotics due to antimicrobial resistance and microbial adaptations has led to the exploration of alternative or complementary therapeutics. In the present study, surface engineered nanosystems (SENS) were developed by conjugation of chitosan with rhamnolipids (RL) through amide linkage. Subsequently, FTIR and NMR analyses affirmed covalent immobilization of RL. SENS exhibited an increase in the particle size and reduction in zeta potential as compared to chitosan nanosystems (CNS). In parallel, first-line antibiotic (ciprofloxacin) was encapsulated in SENS and CNS for augmenting their antimicrobial potential against drug-resistant Salmonella enterica subsp. enterica serotype Typhi. Drug entrapment efficiency for AB-SENS (64 ± 2 %) was higher than AB-CNS. Furthermore, bacterial growth kinetics assay along with colony forming unit (CFU) assay revealed that AB-SENS inhibited the growth of Salmonella sp. even at ½ MIC with restoration of the antibiotic activity. Due to enhanced biofilm penetration ability, the diffusion of entrapped drug from AB-SENS resulted in an effective biofilm disruption to control drug-resistant Salmonella sp. Release kinetics study demonstrated a pH dependent drug release from AB-SENS in simulated gastric fluid (14.2 ± 2 %) and simulated intestinal fluid (28.4 ± 3 %). Hence, our findings suggest that void or drug-loaded SENS can be a versatile synergistic tool to revive the conventional antibiotics for improved treatment outcomes against resistant pathogens.

Chitosan-Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery.

The current study paves the way for improved chemotherapy by creating pH-responsive nanogels (NGs) (GC1 and GC2) loaded with synthetic ruthenium(II) arene complexes to increase biological potency. NGs are fabricated by the conjugation of chitosan (CTS)-biotin biopolymers that selectively target the cancer cells as CTS has the pH-responsive property, which helps in releasing the drug in cancer cells having pH ∼ 5.5, and biotin provides the way to target the cancer cells selectively due to the overexpression of integrin. The synthesized compounds and NGs were thoroughly characterized using various spectroscopic and analytical techniques such as NMR, electrospray ionization-mass spectrometry, Fourier transform infrared, UV-vis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, rheology, Brunauer-Emmett-Teller, and others. NGs displayed exceptional increased efficacy toward cancerous cells with IC50 values ranging from 7.50 to 18.86 μM via induced apoptosis in three human cancer cell lines. Apart from its potency, NGs were found to be highly selective toward cancer cells. Moreover, based on the results of immunoblot analysis, it was observed that the synthesized compounds exhibit a significant increase in the expression of cleaved caspase-3 and a decrease in the expression of the antiapoptotic protein BCL-XL. Interestingly, the complexes were discovered to have the additional capability of catalyzing the conversion of NADH to NAD+, leading to the generation of radical oxygen species within the cells. Additionally, it was discovered that NG-induced apoptosis depends on ROS production and DNA binding. A narrower range of LD50 values (1185.93 and 823.03 μM) was seen after administering NGs to zebrafish embryos in vivo. The results support the use of drug-loaded NGs as potential chemotherapeutic and chemopreventive agents for human cancer cells.

Caffeic Acid in Various Formulations as a Growth and Resistance Regulator of Potato Microclones in &lt;i&gt;in vitro&lt;/i&gt; Culture

The article discusses the influence of caffeic acid (CA), its mix with chitosan (CHT + CA) and chitosan-based conjugate (CHT-CA) on growth and proline content of microclone potato plants (Solanum tuberosum L.) in in vitro culture under optimal conditions and under prolonged osmotic stress caused by polyethylene glycol. Under optimal conditions CHT-CA and CA, acting as moderate strength stressors, accelerate the growth and development of potato microclones and increase the proline accumulation in the stems. Under osmotic stress CA and CHT-CA promote the resistance of potato microclones and maintain their active growth. And such effect persists during the reparation period. The mechanical mix CHT + CA causes inhibition of microclonal plants’ growth and development accompanied by a significant accumulation of proline which is aggravated under stress.

Development and Pharmacokinetic Evaluation of Novasomes for the Trans-nasal Delivery of Fluvoxamine Using Arachidonic Acid-Carboxymethyl Chitosan Conjugate.

Depression is the major mental illness which causes along with loss of interest in daily life, a feeling of hopelessness, appetite or weight changes, anger and irritability. Due to the hepatic first-pass metabolism, the absolute bioavailability of fluvoxamine (FVM) after oral administration is about 50%. By avoiding the pre-systemic metabolism, nasal delivery would boost bioavailability of FVM. Additionally, the absorption is anticipated to occur more quickly than it would via the oral route because of the existence of microvilli and high vasculature. A nonionic surfactant, cholesterol and an arachidonic acid-carboxymethyl chitosan (AA-CMCS) conjugate were used to develop FVM-loaded novasomes. To investigate the effects of surfactant concentration, AA-CMCS conjugate concentration and stirring speed on the novasomes' characteristics, a Box-Behnken design was used. The dependent variables chosen were zeta potential, polydispersity index and particle size. The AA-CMCS conjugate was confirmed by 1H-NMR and FTIR. Using Design Expert software (version 7; Stat-Ease Inc., Minneapolis, MN, USA), novasomes were further optimized. The chosen optimal formulation (NAC8) was made up of AA-CMCS conjugate, Span 60 and cholesterol. Particle size, zeta potential and PDI values for NAC8 formulation were 101 nm, -35 mV and 0.263, respectively. The NAC8 formulation's DSC and TGA analysis demonstrated that the medication had been uniformly and amorphously distributed throughout the novasomes. The NAC8 formulation showed 99% and 90% FVM release and permeation, respectively, and the novasome adherence time was 24 h. An improved antidepressant effect along with five-fold increase in bioavailability of FVM was observed after trans-nasal administration of NAC8 formulation compared to the reference commercially available Flumin® tablets. FVM-loaded novasomes administered via the nasal route may therefore constitute an advancement in the management of depression.