Combining cashew gum with cyclophosphamide in murine melanoma model: A strategy for the reduction of side effects.

The understanding of cancer immunity and antitumor factors generated by natural polysaccharides is not yet fully comprehended. Polysaccharides, like cashew gum (CG), can exhibit immunomodulatory action and may assist in the antitumor process and side effects relieve. This study aimed to determine the antitumor effect of CG alone or in combination with cyclophosphamide (CTX), and its interactions with immune cells, in a murine melanoma model, using the B16-F10 cell line. Tumor growth inhibition, hematological, histopathological, ELISA, flow cytometry, immunofluorescence, and qRT-PCR analyses were performed to elucidate the antitumor potential, involvement of immune cells, and potential toxic effects. CG showed significant tumor growth inhibition, reaching up to 42.9 % alone and 51.4 % in combination with CTX, with mild toxicity to organs. CG enhanced leukocyte count, even in the presence of CTX. Furthermore, CG influenced the activation of tumor-associated macrophages (TAM), characterized by an increase in Il4, as well as a reduction in Ifng, Il1b, Tgfb, and Il6 gene expression. Nevertheless, these effects did not compromise the antitumor activity of CG. In summary, the combination of CG with CTX is a promising approach for leukopenia, one of the most important side effects of cancer treatment and deserves further investigation.

Facile Synthesis of Ni-Doped ZnO Nanoparticles Using Cashew Gum: Investigation of the Structural, Optical, and Photocatalytic Properties.

This work adopted a green synthesis route using cashew tree gum as a mediating agent to obtain Ni-doped ZnO nanoparticles through the sol-gel method. Structural analysis confirmed the formation of the hexagonal wurtzite phase and distortions in the crystal lattice due to the inclusion of Ni cations, which increased the average crystallite size from 61.9 nm to 81.6 nm. These distortions resulted in the growth of point defects in the structure, which influenced the samples' optical properties, causing slight reductions in the band gaps and significant increases in the Urbach energy. The fitting of the photoluminescence spectra confirmed an increase in the concentration of zinc vacancy defects (VZn) and monovacancies (Vo) as Zn cations were replaced by Ni cations in the ZnO structure. The percentage of VZn defects for the pure compound was 11%, increasing to 40% and 47% for the samples doped with 1% and 3% of Ni cations, respectively. In contrast, the highest percentage of VO defects is recorded for the material with the lowest Ni ions concentration, comprising about 60%. The influence of dopant concentration was also reflected in the photocatalytic performance. Among the samples tested, the Zn0.99Ni0.01O compound presented the best result in MB degradation, reaching an efficiency of 98.4%. Thus, the recovered material underwent reuse tests, revealing an efficiency of 98.2% in dye degradation, confirming the stability of the photocatalyst. Furthermore, the use of different inhibitors indicated that •OH radicals are the main ones involved in removing the pollutant. This work is valuable because it presents an ecological synthesis using cashew gum, a natural polysaccharide that has been little explored in the literature.

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.

Novel Scaffold Based on Chitosan Hydrogels/Phthalated Cashew Gum for Supporting Human Dental Pulp Stem Cells.

Hydrogels are structures that have value for application in the area of tissue engineering because they mimic the extracellular matrix. Naturally obtained polysaccharides, such as chitosan (CH) and cashew gum, are materials with the ability to form polymeric networks due to their physicochemical properties. This research aimed to develop a scaffold based on chitosan and phthalated cashew tree gum and test it as a support for the growth of human mesenchymal stem cells. In this study, phthalation in cashew gum (PCG) was performed by using a solvent-free route. PCG-CH scaffold was developed by polyelectrolyte complexation, and its ability to support adherent stem cell growth was evaluated. The scaffold showed a high swelling rate. The pore sizes of the scaffold were analyzed by scanning electron microscopy. Human dental pulp stem cells (hDPSCs) were isolated, expanded, and characterized for their potential to differentiate into mesenchymal lineages and for their immunophenotypic profile. Isolated mesenchymal stem cells presented fibroblastoid morphology, plastic adhesion capacity, and differentiation in osteogenic, adipogenic, and chondrogenic lineages. Mesenchymal stem cells were cultured in scaffolds to assess cell adhesion and growth. The cells seeded on the scaffold showed typical morphology, attachment, and adequate distribution inside the matrix pores. Thus, cells seeded in the scaffold may improve the osteoinductive and osteoconductive properties of these biomaterials.

Insulin-loaded nanoparticles based on acetylated cashew gum/chitosan complexes for oral administration and diabetes treatment.

Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.

pH-responsive phthalate cashew gum nanoparticles for improving drugs delivery and anti-Trypanosoma cruzi efficacy.

Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.

Cashew Gum: A Review of Brazilian Patents and Pharmaceutical Applications with a Special Focus on Nanoparticles.

Natural polysaccharides are structures composed of highly diversified biological macromolecules whose properties have been exploited by a diversity of industries. Until 2018, the polysaccharides market raised more than US $ 12 billion worldwide, while an annual growth forecast of 4.8% is expected by 2026. The food industry is largely responsible for the consumption of this plant-source material, produced by microbiological fermentation. Among the used polysaccharides, gums are hydrocolloids obtained from a variety of sources and in different forms, being composed of salts of calcium, potassium, magnesium and sugar monomers. Their non-toxicity, hydrophilicity, viscosity, biodegradability, biocompatibility and sustainable production are among their main advantages. Although Brazil is amongst the largest producers of cashew gum, reaching 50 tons per year, the polysaccharide is not being used to its full potential, in particular, with regard to its uses in pharmaceuticals. Cashew gum (CG), obtained from Anacardium occidentale L., caught the attention of the industry only in 1970; in 1990, its production started to grow. Within the Brazilian academy, the groups from the Federal University of Ceará and Piauí are devoting the most efforts to the study of cashew gum, with a total of 31 articles already published. The number of patents in the country for innovations containing cashew tree gum has reached 14, including the technological process for the purification of cashew tree gum, comparison of physical and chemical methods for physicochemical characterizations, and optimum purification methodology. This scenario opens a range of opportunities for the use of cashew gum, mainly in the development of new pharmaceutical products, with a special interest in nanoparticles.

Development of purified cashew gum mucoadhesive buccal tablets containing nystatin for treatment of oral candidiasis.

OBJECTIVE: The objective of this work was to prepare mucoadhesive buccal tablets containing nystatin and purified cashew gum for the treatment of oral candidiasis. SIGNIFICANCE: Mucoadhesive buccal tablets containing the drug nystatin are an alternative to oral suspensions, which cause low therapeutic adherence to the treatment of oral candidiasis. Purified cashew gum has been studied as a diluent and mucoadhesive agent in tablets. METHODS: Two batches of mucoadhesive tablets were produced, MT1 and MT 2, containing purified cashew gum, nystatin (500,000 IU), flavoring agent and with or without the presence of lubricant agent. The average weight, mechanical properties, dose uniformity, drug release profile, mucoadhesive properties and antimicrobial activity against Candida albicans were evaluated. RESULTS: Tablets presented average weight of 329.1 ± 3.1 mg (MT1) and 334.6 ± 1.5 mg (MT2), hardness of 9.8 ± 0.8 KgF (MT1) and 8.3 ± 0.4 KgF (MT2), friability of 0.2% (MT1 and MT2), and dose uniformity of 102.20 ± 1.17% (MT1) and 99.06 ± 7.40% (MT2). MT1 and MT2 were able to swell, erode, release the drug and remain adhered to the pig's cheek up to 3 h for batch MT1 and 4 h for batch MT2, and the amount of nystatin released since the beginning of the test in both batches was sufficient to inhibit the growth of the fungus. CONCLUSIONS: Therefore, the proposed formulation proved to be very promising and met all the studied criteria, showing to be ideal for the treatment of oral candidiasis.

Effects of cashew gum and nanoparticles on cooled stallion semen.

BACKGROUND: Cryopreservation of stallion spermatozoa tends to cause plasma membrane damage due to the low ratio of cholesterol to phospholipids. Gums have been suggested as an alternative cryoprotectant to glycerol for stallion spermatozoa. Therefore, the present experiment was designed to verify whether the effect of addition of cashew gum (CG), or nanoparticles (NP) containing CG, to the extender before cooling on sperm quality in stallion semen. Ejaculates from 6 stallions were extended and split between six treatment groups (control, a-tocopherol [TOC], CG1, CG0.5, NP1 and NP0.5), stored in cryotubes at 4 °C. RESULTS: Aliquots were analysed by computer-assisted sperm motility analysis on the day of collection, and after 24 h and 48 h of cold storage. After 48 h, the total motility with NP1 (78.53 + 6.31%) was similar to control 85.79 + 6.31% at 0 h. The same pattern was observed for progressive motility. Membrane integrity assessed by flow cytometer was similar between control, TOC and G1 at all storage times. The DNA fragmentation in the control group increased at all time points, whereas chromatin integrity was maintained after 24 h in TOC and NP0.5 compared to 0 h. There was no increase in the proportion of live spermatozoa producing hydrogen peroxide, but there was a tendency for an increased proportion of spermatozoa in the live superoxide category in CG1 after 24 h cooled storage. CONCLUSIONS: The addition of CG or CG-derived NP to extender for stallion semen was not harmful to the sperm cells.

Kaolinite/cashew gum bionanocomposite for doxazosin incorporation and its release.

Incorporation of drugs in clay minerals has been widely proposed for the controlled-release or increased solubility of drugs. In this context, a bionanocomposite based on kaolinite and cashew gum (Kln/Gum) was synthesized and characterized by X-ray diffraction (XRD), thermal analysis (TG/DTA), and Fourier transform infrared spectroscopy (FTIR). The bionanocomposite was applied to the incorporation and further release of doxazosin mesylate (DB). The influence of solution pH (1-3), adsorbent dose (20-50 mg), initial drug concentration (20.0-70.0 mg L-1), contact time (15-300 min), and temperature (25, 35, and 45 °C) were systematically evaluated. Equilibrium was reached around 60 min, with a maximum adsorption capacity of 31.5 ± 2.0 mg g-1 at a pH of 3.0 and 25 °C. Hydrogen bonding contributed to DB incorporation on the Kln/Gum. In addition, DB maximum amounts of 16.80 ± 0.58 and 77.00 ± 2.46% were released at pH values of 1.2 and 7.4, respectively. These results indicated that the Kln/Gum bionanocomposite is an effective and promising material for the incorporation/release of drugs with similar structures to DB.

Antibacterial application of natural and carboxymethylated cashew gum-based silver nanoparticles produced by microwave-assisted synthesis.

This study presents a green synthesis route to silver nanoparticles (AgNPs) stabilized with cashew gum (CG) or carboxymethylated cashew gum (CCG) using microwave-assisted synthesis and evaluates their antibacterial activity. The antimicrobial activity was measured by determining the minimum inhibitory concentration (MIC) with Staphylococcus aureus and Escherichia coli. In both cases of the presence of CG and CCG, it was found that higher pH lead to more efficient conversion of silver nitrate to AgNPs with well dispersed, spherical and stable particles as well as low crystallinity. CCG-capped AgNPs were slightly smaller (137.0 and 96.3 nm) than those coated with non-modified gum (144.7 and 100.9 nm). The samples presented promising antibacterial activity, especially on Gram-negative bacteria, resulting in significant membrane damage on treated bacteria in comparison to the untreated control, observed by atomic force microscopy. Thus, a quick and efficient synthesis route was applied to produce CGAgNPs and CCGAgNPs with antimicrobial potential.

Anti-proliferative profile of Anacardium occidentale polysaccharide and characterization by AFM.

This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The molar mass of isolated CG was in the order of 103-104 g/mol, with small protein traces present. Polymer characterization by NMR identified key signals correlating to galactose, glucose, rhamnose and acid-related groups. Three distinct conformational stages were observed by AFM. The impact of CG on cell morphology and viability with both tumor and non-tumor cell lines was studied by AFM and 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay respectively. Antiproliferative activity was confirmed for HCT116 (colorectal carcinoma), B16F10 (melanoma) and HL60 (promyelocytic leukemia) cancer cell lines. A change in cell morphology was demonstrated as an increased surface roughness for HL60. Considering that a CG does not exhibit cytotoxicity to non-tumor lines, it can be seen that the CG shows selectivity for tumor cells and can be a promising biomaterial for future studies.

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.

Solvent-free production of phthalated cashew gum for green synthesis of antimicrobial silver nanoparticles.

This work describes a solvent-free method for the chemical modification of cashew gum (Anacardium occidentale L.) using phthalic anhydride in different proportions with different reaction times. Four biopolymers were synthesized and characterized by FTIR, NMR, and elemental analysis. A computational chemistry study was conducted to understand better the reaction. Phthalated cashew gum was used in preparation of silver nanoparticles (AgNPs) by a conventional route, using sodium borohydride (NaBH4) as reducing agent, and for green route. AgNPs were evaluated for antimicrobial activity and characterized by UV-Vis spectroscopy, FTIR, nanoparticle tracking analysis, Zeta Potential analysis, and atomic force microscopy. AgNPs produced by the green route had an average size of 51.9 nm and Zeta Potential of -55.8 mV, and AgNPs produced by the conventional method had an average size of 47.7 nm and Zeta Potential of -39.3 mV. AgNPs synthesized using phthalated cashew gum showed antimicrobial activity against Staphylococcus aureus and Escherichia coli.

Acetylated cashew gum-based nanoparticles for the incorporation of alkaloid epiisopiloturine.

The natural alkaloid epiisopiloturine has recently become the focus of study for various medicinal properties, particularly for its anti-inflammatory and antischistosomal effect. The incorporation of active molecules in natural polymeric matrices has garnered increasing interest during recent decades. A new derivative of cashew gum successfully obtained by gum acetylation has shown great potential as a carrier in controlled drug release systems. In this work, epiisopiloturine was encapsulated in acetylated cashew gum nanoparticles in order to increase solubility and allow slow release, whereas the morphology results were supported by computer simulations. The particles were produced under a variety of conditions, and thoroughly characterized using light scattering and microscopic techniques. The particles were spherical and highly stable in solution, and showed drug incorporation at high levels, up to 55% efficiency. Using a dialysis-based in vitro assay, these particles were shown to release the drug via a Fickian diffusion mechanism, leading to gradual drug release over approximately 6 h. These nanoparticles show potential for the use as drug delivery system, while studies on their potential anti-inflammatory action, as well as toxicity and efficacy assays would need to be performed in the future to confirm their suitability as drug delivery candidates.

Immobilization of antimicrobial trypsin inhibitors onto cashew gum polysaccharide/PVA films.

In this work, films produced by blending cashew gum polysaccharide (CGP) with PVA were used as support for immobilization of trypsin inhibitors with antimicrobial activity obtained from Platypodium elegans (PeTI) and Inga laurina (ILTI). The produced films had a homogeneous macroscopic surface with an absence of bubbles and cracks. SEM of CGP/PVA confirmed the porous structure of these materials, being observed a high incidence of pores with a diameter ranging from 0.4 to 7 µm after swelling in a solution with basic pH. CGP/PVA-F2 presented improved mechanical properties when compared with CGP/PVA-F1, showing higher values of tensile strength and elongation. Results from immobilization efficiency proved that both CGP/PVA formulations were able to entrap trypsin inhibitors. However, the inhibitory activity of the immobilized PeTI was two-fold higher than that observed for ILTI, independently of the film formulation. The release profile of PeTI was similar in both formulations, with an increase in the amount of released inhibitor as a function of time. For ILTI, the CGP/PVA-F2 presented higher release than that from CGP/PVA-F1, achieving a maximum release after 720 min. Also, the released inhibitors showed high stability after 24 h of storage. This study confirmed that CGP/PVA films are versatile and efficient materials to be used as support for immobilization of biomolecules.

Solvent-free synthesis of acetylated cashew gum for oral delivery system of insulin.

Cashew gum (CG) is a biopolymer that presents a favorable chemical environment for structural modifications, which leads to more stable and resistant colloidal systems. The gum was subjected to an acetylation reaction using a fast, simple, solvent-free and low cost methodology. The derivative was characterized by infrared and NMR spectroscopy, elemental analysis, coefficient of solubility and zeta potential. The modified biopolymer was used as a platform for drug delivery systems using insulin as a model drug. Nanoparticles were developed through the technique of polyelectrolytic complexation and were characterized by size, surface charge, entrapment efficiency and gastrointestinal release profile. The nanoparticles presented size of 460 nm with a 52.5% efficiency of entrapment of insulin and the electrostatic stabilization was suggested by the zeta potential of + 30.6 mV. Sustained release of insulin was observed for up to 24 h. The results showed that acetylated cashew gum (ACG) presented potential as a vehicle for sustained oral insulin release.

Cashew gum and maltrodextrin particles for green tea (Camellia sinensis var Assamica) extract encapsulation.

Cashew gum and maltodextrin microcapsules containing green tea leaf extracts were made using a spray-dryer. Green tea extracts were submitted to cytotoxicity analysis and characterization of bioactive compounds. Three formulations of microcapsules were performed, which were then submitted to characterization through morphological study, particle diameter and distribution, zeta potential, Exploratory Differential Calorimetry, entrapment efficiency, dissolution test and X-ray diffraction. The extract had a high bioactive compound content and no cytotoxicity was observed. The amorphous microcapsules presented irregular shapes with a circular predominance and dentate surface, mean diameters varying from 2.50 to 3.64 µm, solubility ranging from 63% to 72.66%. Low values of microencapsulation efficiency, zeta potencial and dissolution profile were observed. The microparticles based on the dry extract of green tea present potential as a food ingredient and as a promoter of health benefits.

Enhancing stability of echium seed oil and beta-sitosterol by their coencapsulation by complex coacervation using different combinations of wall materials and crosslinkers.

Intake of omega-3 fatty acids and phytosterols aids in the reduction of cholesterol and serum triglycerides. However, both fatty acids and phytosterols are susceptible to oxidation. This work coencapsulated echium oil (source of stearidonic and alpha-linolenic fatty acids) and beta-sitosterol (phytosterol) by complex coacervation using different combinations of wall materials, and sinapic acid (SA) and transglutaminase as crosslinkers. High encapsulation yields were obtained (29-93% for SA; 68-100% for the mixture of oil and phytosterols) and retention of 49-99% and 16% for encapsulated and free SA, at 30 days-storage. Treatment with gelatin-arabic gum and 0.075 g SA/g gelatin showed the best results: 0.07 mg MDA/g capsule, and retention of 96, 90 and 74% for alpha-linolenic, stearidonic acid and beta-sitosterol at 30 days of storage, respectively. Thus, coencapsulation of echium oil and phytosterol using SA as the crosslinker was possible, obtaining effective vehicles for protection and application of these compounds in foods.