Gastroprotective activity and physicochemical analysis of carboxymethylated gum from Anadenanthera colubrina.

Biotechnological advancements require the physicochemical alteration of molecules to enhance their biological efficacy for the effective treatment of gastric ulcers. The study aimed to produce a polyelectrolytic compound from red angico gum (AG) by carboxymethylation, evaluate its physicochemical characteristics and investigate gastric protection against ethanol-induced ulcers. AG and carboxymethylated angico gum (CAG) were characterized by Fourier transform infrared spectroscopy, determination of the degree of substitution and gel permeation chromatography (GPC) and 13C NMR techniques. The results demonstrated that the modification of the polymer was satisfactory, presenting conformational changes e improving the interaction with the gastric mucosa. AG and CAG reduced macroscopic and microscopic damage such as edema, hemorrhage and cell loss caused by exposure of the mucosa to alcohol. Both demonstrated antioxidant activity in vitro, and in vivo, pretreatment with gums led to the restoration of superoxide dismutase and glutathione levels compared to the injured group. Concurrently, the levels of malondialdehyde and nitrite decreased. Atomic force microscopy showed that CAG presented better conformational properties of affinity and protection with the gastric mucosa compared to AG in the acidic pH. Based on our findings, it is suggested that this compound holds promise as a prospective product for future biotechnological applications.

Influence of Reduction with NaBH4 and HCl in Obtaining Amino Derivatives of Cashew Gum and Cytotoxic Profile.

Tree-exuded gums are natural polymers that represent an abundant raw material in the food and pharmaceutical industries. The cashew gum can be obtained by exudation of trees of the genus Anacardium, a native species of the Brazilian northeast; its polymer consists of monosaccharide units propitious to the action of chemical reactions that tend to improve their intrinsic characteristics among them, as the degree of hydro-solubility. The objective of this work was to modify the exudate gum of Anacardium occidentale (cashew gum (CG)) through an amine reaction. The modification was confirmed by Nuclear Magnetic Resonance (1H NMR), infrared spectroscopy (FTIR), gel permeation chromatography (GPC), zeta potential, and thermogravimetric analysis (TG). In addition, the chemical modification altered the molar mass and surface charge of the CG, and the amino group binding to the CG polymers was confirmed by FTIR spectra. In addition, cytotoxicity tests were performed where cell viability was estimated by an MTT assay on RAW 264.7 macrophages. Through these tests, it was found that the amine caused an increase in the thermal stability of the amino compounds and did not present cytotoxic potential at concentrations below 50.0 mg/L.

Eco-friendly synthesis of phthalate angico gum towards nanoparticles engineering using Quality by Design (QbD) approach.

We developed a new hydrophobic polymer based on angico gum (AG), and we produced new nanoparticles to expand the applications of natural polysaccharides in nanomedicine. Phthalate angico gum (PAG) was characterized by 1H NMR, FTIR, elementary analysis, solubility, XRD, and TG. PAG was a hydrophobic and semi-crystalline material, a relevant characteristic for drug delivery system applications. As a proof of concept, nevirapine (NVP) was selected for nanoparticles development. Plackett-Burman's experimental design was used to understand the influence of several factors in nanoparticles production. PAG proved to be a versatile material for producing nanoparticles with different characteristics. Optimized nanoparticles were produced using desirability parameters. NVP-loaded PAG nanoparticles formulation showed 202.1 nm of particle size, 0.23 of PDI, -17.1 of zeta potential, 69.8 of encapsulation efficiency, and promoted modified drug release for 8 h. Here we show that PAG presents as a promising biopolymer for drug delivery systems.

Dual responsive dextran-graft-poly (N-isopropylacrylamide)/doxorubicin prodrug via Schiff base reaction.

Stimulus-responsive nanoparticles stand out in studies for cancer treatment since these systems can promote a selective release of the drug in tumor tissues and cells, minimizing the effects caused by conventional chemotherapy. Dextran-graft-poly (N-isopropylacrylamide) copolymers were synthesized via Schiff base formation. The synthesis of copolymers was confirmed by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (NMR) and the analyses of dynamic light scattering (DLS) showed that the copolymers were thermal and pH dual-responsive. The chemotherapy drug doxorubicin (DOX) was conjugated to the copolymers via Schiff base formation, obtaining nanoparticles by self-assembling with size smaller than 130 nm. A higher percentage of doxorubicin was released at pH 5.0 (59.1 ± 2.1%) compared to physiological pH (34.9 ± 4.8%), confirming a pH-sensitive release profile. The in vitro cytotoxicity assay demonstrated that DOX-loaded nanoparticles can inhibit cancer cell proliferation and promote reduced cytotoxicity in non-tumor cells. The D45kP30k-DOX nanoparticles induced morphological changes in HCT-116 cells suggesting cell death and the cell uptake assay indicated that the nanoparticles can be internalized by endocytosis. Therefore, DOX-loaded nanoparticles exhibited potential as smart systems for cancer treatment.

Protective effect against gastric mucosa injury of a sulfated agaran from Acanthophora spicifera.

In this study, a polysaccharide from marine alga Acanthophora spicifera (PAs) was isolated and structurally characterized. Its protective potential against chemically-induced gastric mucosa injury was evaluated. The gel permeation chromatography experiments and spectroscopy spectrum showed that PAs is a sulfated polysaccharide with a high molecular mass (6.98 × 105g/mol) and degree of sulfation of 1.23, exhibiting structural characteristic typical of an agar-type polysaccharide. Experimental results demonstrated that PAs reduced the hemorrhagic gastric injury, in a dose-dependent manner. Additionally, PAs reduced the intense gastric oxidative stress, measured by glutathione (GSH) and malondialdehyde (MDA) levels. PAs also prevented the reduction of mucus levels adhered to the gastric mucosa, promoted by the aggressive effect of ethanol. In summary, the sulfated polysaccharide from A. spicifera protected the gastric mucosa through the prevention of lipid peroxidation and enhanced the defense mechanisms of the gastric mucosa, suggesting as a promising functional food as gastroprotective agent.

Poly(ε-caprolactone) grafted cashew gum nanoparticles as an epirubicin delivery system.

Polysaccharide based copolymers have been the focus of several research, particularly for the development of drug delivery systems. This study reports on the preparation of nanoparticles from an amphiphilic copolymer obtained by the poly(ε-caprolactone) graft in the structure of cashew gum, via ring-opening polymerization. The synthesis of copolymers was confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. The copolymers exhibit self-organization capability in water, with critical association concentration of 42 and 50 µg mL-1. The nanoparticle hydrodynamic diameters (212 and 202 nm) revealed a decreasing trend with increasing poly(ε-caprolactone) graft percentage. Epirubicin was used as an anticancer drug model and incorporated into the nanoparticles. The encapsulation efficiency reached 50% and 5.0% drug load. Nanoparticles showed an epirubicin controlled release profile, with maximum release of 93.0 ± 4.0% in 72 h, as well as excellent biocompatibility, according to hemolysis and cytotoxicity assays.

Microwave-initiated rapid synthesis of phthalated cashew gum for drug delivery systems.

Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, 1H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of -31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease.

Eco-friendly synthesis of an alkyl chitosan derivative.

Chitosan (CH) was N-alkylated via Schiff base formation and further reduced via sodium borohydride. The reaction was carried out at room temperature, in a homogeneous aqueous medium, using as a source of alkyl group an essential oil (Eucalyptus staigeriana) containing an unsaturated aldehyde (3,7-dimethylocta-2,6-dienal). Derivatives were characterized by Infrared Spectroscopy, proton and carbon Nuclear Magnetic Resonance, XRD, particle size distribution and zeta potential. Chitosan hydrophobization evidence was given by FTIR as new bands at 2929 cm-1 due to methyl groups, along with the presence of strong band at 1580 cm-1 owing to N substitution. Moreover, carbon and proton NMR corroborated the insertion of methyl groups in chitosan backbone. The degree of substitution was found to be in the range 0.69-1.44. X-ray diffractograms revealed that the insertion of alkyl substituents in chitosan backbone led to a less crystalline material. Data from antibacterial activity revealed that chitosan and derivatives were effective against Gram-positive bacteria, whereby derivatives exhibited greater inhibitory effect than CH. Derivatives are likely candidates for use as carriers for active principles of interest of food, pharmacy and medicine.

A new heterofunctional support for enzyme immobilization: PEI functionalized Fe3O4 MNPs activated with divinyl sulfone. Application in the immobilization of lipase from Thermomyces lanuginosus.

Lipase from Thermomyces lanuginosus (TLL) was immobilized onto a novel heterofunctional support, divinyl sulfone (DVS) superparamagnetic nanoparticles (SPMNs) functionalized with polyethyleneimine (PEI). Particle size and zeta potential measurements, elemental analysis, X-ray powder diffraction, magnetic measurements, and infrared spectroscopy analysis were used to characterize the TLL preparations. At pH 10, it was possible to achieve 100 % of immobilization yield in 1 h. The immobilization pH gives TLL preparations with different stabilities; indeed the TLL preparation immobilized at pH 5.0 was the most stable during the thermal inactivation at all pH values. For the hydrolysis of racemic methyl mandelate, the nanobiocatalysts immobilized at pH 5.0 and blocked with ethylenediamine (EDA) and ethanolamine (ETA) obtained good enantioselectivities (68 % and 72 %, respectively) with high catalytic activities in the reaction medium at pH 7.0. The operational stability of the systems was evaluated in the esterification reaction of benzyl alcohol, obtaining up to 61 % conversion after the seventh reaction cycle. These results show that SPMN@PEI-DVS support is a robust strategy for the easy and rapid recovery of the nanobiocatalyst by applying a magnetic field, showing great potential for industrial applications.

Influence of galactomannan molar mass on particle size galactomannan-grafted-poly-N-isopropylacrylamide copolymers.

In order to synthesize nanoparticles of galactomannan-g-poly-N-isopropylacrylamide copolymers, galactomannan from fava d'anta was partially hydrolyzed using hydrochloric acid. Degradation reduced the molar mass and increase mannose/galactose molar ratio. This study shows that high molar mass of galatomannan lead to formation of copolymers with particle size in the order of micrometer, however reducing molar mass from 106 to 104 g mol-1, thermo-sensitive copolymer with low critical aggregation concentration, transition temperature close to body temperature (37 °C) and particle size in the range of 300-170 nm can be obtained. As a proof of concept, partially degraded galactomannan-g-NIPAm copolymer was used to incorporated indomethacin. Good encapsulation efficiency and a controlled release were observed indicating that this material has potential to be used as nanocarrier system.

Self-assembling cashew gum-graft-polylactide copolymer nanoparticles as a potential amphotericin B delivery matrix.

Amphotericin B is an antibiotic used in the treatment of fungal disease and leishmania; however, it exhibits side effects to patients, hindering its wider application. Therefore, nanocarriers have been investigated as delivery systems for amphotericin B (AMB) in order to decrease its toxicity, besides increase bioavailability and solubility. Amphiphilic copolymers are interesting materials to encapsulate hydrophobic drugs such as AMB, hence copolymers of cashew gum (CG) and l-lactide (LA) were synthesized using two different CG:LA molar ratios (1:1 and 1:10). Data obtained revealed that copolymer nanoparticles present similar figures for particle sizes and zeta potentials; however, particle size of encapsulated AMB increases if compared to unloaded nanoparticles. The 1:10 nanoparticle sample has better stability although higher polydispersity index (PDI) if compared to 1:1 sample. High amphotericin (AMB) encapsulation efficiencies and low hemolysis were obtained. AMB loaded copolymers show lower aggregation pattern than commercial AMB solution. AMB loaded nanoparticles show antifungal activities against four C. albicans strains. It can be inferred that cashew gum/polylactide copolymers have potential as nanocarrier systems for AMB.

Biopolymer Extracted from Anadenanthera colubrina (Red Angico Gum) Exerts Therapeutic Potential in Mice: Antidiarrheal Activity and Safety Assessment.

Anadenanthera colubrina var. cebil (Griseb.) Altschul (Fabaceae family), commonly known as the red angico tree, is a medicinal plant found throughout Brazil's semi-arid area. In this study, a chemical analysis was performed to investigate the antidiarrheal activity and safety profile of red angico gum (RAG), a biopolymer extracted from the trunk exudate of A. colubrina. Upon FT-IR spectroscopy, RAG showed bands in the regions of 1608 cm-1, 1368 cm-1, and 1029 cm-1, which relate to the vibration of O-H water molecules, deformation vibration of C-O bands, and vibration of the polysaccharide C-O band, respectively, all of which are relevant to glycosidic bonds. The peak molar mass of RAG was 1.89 × 105 g/mol, with the zeta potential indicating electronegativity. RAG demonstrated high yield and solubility with a low degree of impurity. Pre-treatment with RAG reduced the total diarrheal stool and enteropooling. RAG also enhanced Na+/K+-ATPase activity and reduced gastrointestinal transit, and thereby inhibited intestinal smooth muscle contractions. Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that RAG can interact with GM1 receptors and can also reduce E. coli-induced diarrhea in vivo. Moreover, RAG did not induce any signs of toxicity in mice. These results suggest that RAG is a possible candidate for the treatment of diarrheal diseases.

Development of amphotericin B-loaded propionate Sterculia striata polysaccharide nanocarrier.

This work was aimed at the production and characterization of a new nanocarrier based on a Sterculia striata polysaccharide (SSP) modified via acylation reaction with propionic anhydride. Nanocapsules of propionated SSP (PSSP) were produced via spontaneous nanoemulsification process and tested as a potential amphotericin B (AMB) nanocarrier. Stable nanoparticles with a very low polydispersity index (0.08-0.29) and high zeta potential (ζ -42.7 to -53.8 mV) were obtained. Particle size was dependent on the degree of substitution and ranged from 205 to 286 nm. A nanocapsule with a degree of substitution (DS) of 2.53 (NCP 2.53) was selected for encapsulation, biocompatibility, and antifungal evaluation against Candida albicans strains. A maximum of 98.3% AMB encapsulation was achieved. Encapsulated AMB was in its monomeric form and showed good biocompatibility and antifungal activity against four C. albicans strains. Data indicate that PSSP has potential as a nanocarrier system for AMB.

Pickering emulsions stabilized with cashew gum nanoparticles as indomethacin carrier.

Polysaccharide nanoparticles with potential to stabilize Pickering emulsions have been recently object of many research. Acetylated cashew gum with different degrees of substitution has been used in this work, in the pursuit of obtaining stable Pickering emulsions. Acetylated cashew gum was characterized by infrared and nuclear resonance spectroscopy. Effects of cashew gum derivative acetyl content, droplet size, ionic strength, zeta potential on emulsion properties were investigated. As a proof of concept, indomethacin was encapsulated in droplets and its release profile determined. Data obtained revealed droplet sizes in the range 269-312 nm, with unimodal size distribution and zeta potential values from -46 Mv to -48 Mv. Encapsulation efficiencies were in the range 26-52%, a steady release profile reached in 3 h, releasing maximal 75% IND.

Hydrophobization of cashew gum by acetylation mechanism and amphotericin B encapsulation.

Cashew gum (GC) is a polysaccharide whose structural modification has the potential to extend its applications on varied fields such as to the formation of self-organized nanoparticulated systems. In this work, a 23 factorial design was carried out, aiming at evaluation of the influence of the reactional parameters of an acetylation reaction on the final properties of cashew gum. The effects of temperature, reaction time and amount of acetylating agent on the reaction yield and degree of GC acetylation were investigated. Data obtained revealed that the aforementioned parameters influenced both yield and degree of acetylation. Statistical analysis showed that the different derivatives had their variables influenced mainly by temperature and interaction effect between the factors time and quantity of acetylating agent. Acetylated derivatives were obtained with yield higher than 90% and degrees of acetylation above 2.42. Data on the formation of self-organized systems, revealed particle sizes in the range 190-300nm, where smaller particle sizes were obtained for derivatives with acetylation degrees lower than 1.5. Release profiles of Amphotericin-B incorporated in derivative nanoparticles, yielded 70% encapsulation efficiency and long release profiles, corroborating their potential application to delivery of hydrophobic active principles.

The potential of cashew gum functionalization as building blocks for layer-by-layer films.

Cashew gum (CG), an exudate polysaccharide from Anacardium occidentale trees, was carboxymethylated (CGCm) and oxidized (CGO). These derivatives were characterized by FTIR and zeta potential measurements confirming the success of carboxymethylation and oxidation reactions. Nanostructured multilayered films were then produced through layer-by-layer (LbL) assembly in conjugation with chitosan via electrostatic interactions or Schiff bases covalent bonds. The films were analyzed by QCM-D and AFM. CG functionalization increased the film thickness, with the highest thickness being achieved for the lowest oxidation degree. The roughest surface was obtained for the CGO with the highest oxidation degree due to the predominance of covalent Schiff bases. This work shows that nanostructured films can be assembled and stabilized by covalent bonds in alternative to the conventional electrostatic ones. Moreover, the functionalization of CG can increase its feasibility in multilayers films, widening its potential in biomedical, food industry, or environmental applications.

Matrix Effect on the Spray Drying Nanoencapsulation of Lippia sidoides Essential Oil in Chitosan-Native Gum Blends.

Essential oils have many applications in the pharmaceutical, chemical, and food fields, however, their use is limited to the fact that they are very labile, requiring their a priori encapsulation, aiming to preserve their properties.This work reports on the preparation of chitosan-gum nanoparticles loaded with thymol containing Lippia sidoides essential oil, using exudates of Anacardium Occidentale (cashew gum), Sterculia striata (chichá gum), and Anadenanthera macrocarpa trees (angico gum). Nanoparticles were produced by spray drying an emulsion of L. sidoides essential oil and aqueous solution of gums with different chitosan : gum ratios. Samples were characterized by FTIR and UV/VIS spectroscopy, particle size, volume distribution, and zeta potential. The FTIR spectrum showed the main signals of chitosan and the gums. Data obtained revealed that the samples had sizes in the nano range, varying from 17 nm to 800 nm. The zeta potential varied from + 30 mV to - 40 mV. Nanoparticle loading values varied from 6.7 % to 15.6 %, with an average encapsulating efficiency of 62 %, where the samples with high ratios of cashew gum and chichá gum presented high oil loading values. The data revealed that both the chitosan : gum ratio and polysaccharide characteristics play major roles in nanoencapsulation processes.

Synthesis and characterization of non-toxic and thermo-sensitive poly(N-isopropylacrylamide)-grafted cashew gum nanoparticles as a potential epirubicin delivery matrix.

Cashew gum (CG) was grafted with N-isopropylacrylamide (NIPA) by radical polymerization to originate a stimuli-sensitive copolymer for drug delivery purposes. NMR and IR spectroscopy confirmed the insertion of NIPA onto the cashew gum chains. The graft copolymer (CG:NIPA) demonstrated thermal responsiveness. The critical aggregation concentration of the copolymers at 25°C was higher than at 50°C. At temperatures lower than the LCST, the nanoparticle size ranged from 12 to 21nm, depending on the CG:NIPA ratio, but above the LCST the particles aggregated, increasing the particle size. Regarding the potential for future oral application, the nanoparticles showed no cytotoxic activity against the Caco-2 and HT29-MTX intestine cell lines. Epirubicin was encapsulated into nanoparticles of CG-NIPA (1:1), resulting in a 64% association efficiency and 22% loading capacity. Thus, the CG:NIPA graft copolymer demonstrates good potential for used in controlled drug delivery systems.

Sulfated polysaccharide fraction from marine algae Solieria filiformis: Structural characterization, gastroprotective and antioxidant effects.

A sulfated polysaccharide (SFP) fraction from the marine alga Solieria filiformis was extracted and submitted to microanalysis, molar mass estimation and spectroscopic analysis. We evaluated its gastroprotective potential in vivo in an ethanol-induced gastric damage model and its in vitro antioxidant properties (DPPH, chelating ferrous ability and total antioxidant capacity). Its chemical composition revealed to be essentially an iota-carrageenan with a molar mass of 210.9kDa and high degree of substitution for sulfate groups (1.08). In vivo, SFP significantly (P<0.05) reduced, in a dose dependent manner, the ethanol-induced gastric damage. SFP prevents glutathione consume and increase of malondialdehyde and hemoglobin levels. SFP presented an IC50 of 1.77mg/mL in scavenging DPPH. The chelating ferrous ability was 38.98%, and the total antioxidant capacity was 2.01mg/mL. Thus, SFP prevents the development of ethanol-induced gastric damage by reducing oxidative stress in vivo and possesses relevant antioxidant activity in vitro.

Sulfated polysaccharide from the marine algae Hypnea musciformis inhibits TNBS-induced intestinal damage in rats.

Sulfated polysaccharides extracted from seaweed have important pharmacological properties. Thus, the aim of this study was to characterize the sulfated polysaccharide (PLS) from the algae Hypnea musciformis and evaluate its protective effect in colitis induced by trinitrobenzene sulfonic acid in rats. The sulfated polysaccharide possess a high molecular mass (1.24×10(5)gmol(-1)) and is composed of a κ-carrageenan, as depicted by FT-IR and NMR spectroscopic data. PLS was administered orally (10, 30, and 60mg/kg, p.o.) for three days, starting before TNBS (trinitrobenzene sulfonic acid) instillation (day 1). The rats were killed on day three, the portion of distal colon (5cm) was excised and evaluated macroscopic scores and wet weight. Then, samples of the intestinal were used for histological evaluation and quantification of glutathione, malonyldialdehyde acid, myeloperoxidase, nitrate/nitrite and cytokines. Our results demonstrate that PLS reduced the colitis and all analyzed biochemical parameters. Thus, we concluded that the PLS extracted from the marine algae H. musciformis reduced the colitis in animal model and may have an important promising application in the inflammatory bowel diseases.