RESUMO
In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.
Assuntos
Doxorrubicina , Galactose , Mananas , Nanoconjugados , Doxorrubicina/farmacologia , Doxorrubicina/química , Mananas/química , Mananas/farmacologia , Galactose/química , Galactose/análogos & derivados , Humanos , Nanoconjugados/química , Concentração de Íons de Hidrogênio , Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.
Assuntos
Mucosa Esofágica , Refluxo Gastroesofágico , Humanos , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/prevenção & controle , Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/patologia , Mucosa Esofágica/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Permeabilidade , Impedância Elétrica , Administração Tópica , Biopolímeros , Idoso , Fluoresceína/administração & dosagem , Esôfago/efeitos dos fármacos , Esôfago/patologia , Esôfago/metabolismo , Azia/tratamento farmacológico , Azia/prevenção & controle , Relevância ClínicaRESUMO
The present work explores the esterification reaction in the polysaccharide extracted from the seaweed Gracilaria birdiae and investigates its antioxidant potential. The reaction process was conducted with phthalic anhydride at different reaction times (10, 20 and 30 min), using a molar ratio of 1:2 (polymer: phthalic anhydride). Derivatives were characterized by FTIR, TGA, DSC and XRD. The biological properties of derivatives were investigated by assays of cytotoxicity and antioxidant activity (2,2-diphenyl-1-picrylhydroxyl - DPPH and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt - ABTS). The results obtained by FT-IR confirmed the chemical modification, there was a reduction related to the presence of carbonyl and hydroxyl groups when compared to the in nature polysaccharide spectrum. TGA analysis showed a change in the thermal behavior of the modified materials. X-ray diffraction, it was shown that the in nature polysaccharide appeared as an amorphous material, while the material obtained after the chemical modification process had increased crystallinity, due to the introduction of phthalate groups. For the biological assays, it was observed that the phthalate derivative was more selective than the unmodified material for the murine metastatic melanoma tumor cell line (B16F10), revealing a good antioxidant profile for DPPH and ABTS radicals.
Assuntos
Antineoplásicos , Gracilaria , Animais , Camundongos , Antioxidantes/química , Anidridos Ftálicos , Galactanos , Espectroscopia de Infravermelho com Transformada de Fourier , Antineoplásicos/química , Polissacarídeos/químicaRESUMO
Aminated poly(N-isopropylacrylamide) (PNIPAm-NH2) was grafted onto oxidized galactomannan polysaccharide extracted from Delonix regia (OXGM) via Schiff base reaction by a simple, rapid synthetic route, deprived of the use of organic solvents. Grafting was confirmed by FTIR and 1H NMR and the self-organizing ability of the obtained nanoparticle copolymers was investigated by dynamic light scattering (DLS). The minimum concentration required for self-organization (CAC) at 25 °C was higher than at 50 °C. Lower critical solution temperature (LCST) was in the range 34-40 °C, depending on both inserted PNIPAm-NH2 molar mass and on the presence of reduced imine bond. Synthesized copolymers are promising candidates for drug delivery as they show good cell viability, particle size around 250 nm and transition temperature closer to that of human body. Reaction success points out to the possibility of use free aldehyde groups of oxidized polysaccharide, not used in the copolymerization, to form a pro-drug with substances that possess NH2 groups in their structure, such as doxorubicin.
Assuntos
Resinas Acrílicas/química , Materiais Biocompatíveis/síntese química , Fabaceae/química , Mananas/química , Galactose/análogos & derivados , Polimerização , Bases de Schiff/química , Sementes/química , Temperatura de TransiçãoRESUMO
In the present work, we investigated the minimal inhibitory concentration (MIC) against fungal strains (Fonsecaea pedrosoi, Microsporum canis, Candida albicans, Cryptococcus neoformans), and cytotoxicity to normal cell lines for modified red angico gum (AG) with eterifying agent N-chloride (3-chloro-2-hydroxypropyl) trimethylammonium (CHPTAC). Quaternized ammonium groups were linked to AG backbone using N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride. The chemical features of the quaternized gum derivatives (QAG) were analyzed by: FTIR, elemental analysis, Zeta potential and gel permeation chromatography. The angico quaternizated gum presented a degree of substitution (DS) of 0.22 and Zeta potential of +36.43. For the antifungal test, it was observed that unmodified gum did not inhibit fungal growth. While, QAG inhibited the growth of most fungi used in this study. By AFM technique QAG interacted with the fungal surface, altering wall roughness significantly. The probable affinity of fragments of the QAG structure for the fungal enzyme 5I33 (Adenylosuccinate synthetase) has been shown by molecular docking. Low cytotoxicity was observed for polymers (unmodified gum and QAG). The results demonstrate that the quaternized polymer of AG presented in this study is a quite promising biomaterial for biotechnological applications.
Assuntos
Antifúngicos , Citotoxinas , Inibidores Enzimáticos , Fabaceae/química , Proteínas Fúngicas , Fungos/enzimologia , Simulação de Acoplamento Molecular , Polissacarídeos , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Citotoxinas/química , Citotoxinas/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/química , Células HEK293 , Humanos , Ligases/antagonistas & inibidores , Ligases/química , Camundongos , Polissacarídeos/química , Polissacarídeos/farmacologiaRESUMO
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.
Assuntos
Anacardium , Antibacterianos , Nanopartículas Metálicas , Gomas Vegetais , Prata , Antibacterianos/administração & dosagem , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Micro-Ondas , Gomas Vegetais/administração & dosagem , Gomas Vegetais/química , Prata/administração & dosagem , Prata/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
A sulfated polysaccharide from the red algae Gelidiella acerosa (GaSP) was obtained through enzymatic extraction and subjected to chemical characterization by HPSEC, elemental microanalysis, FT-IR and NMR spectroscopies. The GaSP anticoagulant activity was investigated through APTT and PT tests and platelet aggregation assessed by turbidimetry. The antithrombotic and hemorrhagic activities were evaluated by venous thrombosis and hemorrhagic tendency models, respectively. FT-IR and NMR demonstrated that GaSP is a sulfated agaran. HPSEC and elemental microanalysis revealed a peak molar mass of 284.8 kDa and a degree of sulfation of 0.63, respectively. This molecule prolonged the coagulation time in 2.1 times and inhibited the platelet aggregation by 45%. Furthermore, it showed significant dose-dependent antithrombotic effect of 40%, 64% and 80% at 0.1, 0.5 and 1 mg/kg, respectively, without hemorrhage. These results suggest that GaSP has promising antithrombotic.
Assuntos
Polissacarídeos/química , Polissacarídeos/farmacologia , Rodófitas/química , Sulfatos/química , Animais , Anticoagulantes/química , Anticoagulantes/farmacologia , Testes de Coagulação Sanguínea , Feminino , Fibrinolíticos/química , Fibrinolíticos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Peso Molecular , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologiaRESUMO
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.
Assuntos
Anacardium/química , Microscopia de Força Atômica , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Gomas Vegetais/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: There are many reports of pharmacological activities of extracts and fractions of different vegetable-derived products in the scientific literature and in folk medicine. Ethnopharmacological use of these products by various communities continues to be extensively explored, and they account for more than half of all medications used worldwide. Polysaccharides (PLS) extracted from plants such as Morinda Citrifolia Linn present therapeutic potential in treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). AIM OF THE STUDY: To evaluate the anti-inflammatory action of Noni-PLS against the intestinal damage in UC induced by acetic acid in mice. MATERIALS AND METHODS: In acetic acid-induced colitis, the mice were treated intraperitoneally (ip) with Noni-PLS (0.1, 0.3, and 3.0â¯mg/kg) or subcutaneously (sc) with dexamethasone (2.0â¯mg/kg) 30â¯min before euthanasia to determine the best dose of Noni-PLS with an anti-inflammatory effect in the course of UC. The colonic tissue samples were collected for macroscopic, wet weight, microscopic and biochemical (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), nitrate/nitrite (NO3/NO2), cytokines, cyclooxygenase (COX-2) and inducible nitric oxide (iNOS)) analyses. RESULTS: Treatment with Noni-PLS reduced the intestinal damage induced by acetic acid as it reduced macroscopic and microscopic scores and the wet weight of the colon. In addition, MPO activity and levels of GSH, MDA, NO3/NO2, pro-inflammatory cytokines, and COX-2 expression reduced. CONCLUSIONS: This study suggests that Noni-PLS exhibits anti-inflammatory action against intestinal damage by reducing inflammatory cell infiltration, oxidative stress, pro-inflammatory action of cytokines, COX-2 and iNOS expression in the inflamed colon. Noni-PLS shows therapeutic potential against inflammatory disorders like UC.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Morinda , Polissacarídeos/uso terapêutico , Ácido Acético , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Frutas , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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 6â¯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.
Assuntos
4-Butirolactona/análogos & derivados , Alcaloides/química , Anacardium/química , Portadores de Fármacos/química , Imidazóis/química , Nanopartículas/química , Gomas Vegetais/química , 4-Butirolactona/química , Acetilação , Configuração de Carboidratos , Liberação Controlada de Fármacos , Modelos Moleculares , SolubilidadeRESUMO
Polysaccharides extracted from plants are very promising molecules in the field of pharmacotherapy. Knowing this, the aim of this study was to extract, characterize and evaluate the action of the polysaccharide of Morinda citrifolia Linn (Noni-PLS) in biological models of inflammatory processes. The characterization tests shown that sample refers to a heteropolysaccharide composed mainly of homogalacturonan and rhamnogalacturonan. This polysaccharide at dose of 10â¯mg/kg, when tested in our models of inflammation, showed significant activity in reducing carrageenan-induced paw oedema as well as all mediators edemas. This polysaccharide was able to inhibit the migration of leukocytes to the site of inflammation, and still reduced inflammatory nociception tests. This results, allows us to conclude that the polysaccharide extracted from Morinda citrifolia linn has anti-inflammatory potential since it reversed inflammatory parameters such as edema, leukocyte migration and nociception.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Edema/tratamento farmacológico , Morinda/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Carragenina , Edema/induzido quimicamente , Edema/patologia , Masculino , Camundongos , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificaçãoRESUMO
Nanoprecipitation and dialysis methods were employed to obtain nanoparticles (NPs) of acetylated cashew gum (ACG). NPs synthesized by dialysis showed greater average size compared to those synthesized by nanoprecipitation, but they presented improved stability and yield. NPs were loaded with diclofenac diethylamine and the efficiency of the drug incorporation was over 60% for both methods, for an ACG:NP a weight ratio of 10:1. The cytotoxicity assay demonstrated that the NPs had no significant effect on the cell viability, verifying their biocompatibility. The release profile for the diclofenac diethylamine associated with the ACG-NPs showed a more controlled release compared to the free drug and a Fickian diffusion mechanism was observed. Transdermal permeation reached 90% penetration of the drug.
Assuntos
Diclofenaco/análogos & derivados , Diclofenaco/administração & dosagem , Dietilaminas/administração & dosagem , Nanopartículas/química , Gomas Vegetais/síntese química , Acetilação , Administração Cutânea , Anacardium , Linhagem Celular , Diclofenaco/química , Dietilaminas/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Nanopartículas/toxicidade , Tamanho da Partícula , Gomas Vegetais/toxicidadeRESUMO
OBJECTIVE: The aim of this study was determine the chemical composition and thermal behavior of Thermafil (TH), Microseal Cone (MC), Microseal Microflow (MF), Obtura (OB) and Obtura Flow (OF). In addition, their thermal behavior in response to temperature variations was studied by differential scanning calorimetry (DSC) to determine the temperature at which gutta-percha switches from the beta to alpha form, and from the alpha to the amorphous phase. MATERIALS AND METHODS: The organic and inorganic fractions were separated by dissolution in chloroform. Gutta-percha (GP) was precipitated with acetone. The inorganic fraction was analyzed via Elemental Microanalysis. Energy Dispersive X-ray Microanalysis and X-ray Diffraction were used to identify the chemical elements and compounds (BaSO4 and ZnO). Thermal analysis was conducted using DSC. RESULTS: The organic and inorganic fractions ranged from 21.3% and 26.9% of weights, respectively. MC and MF showed the highest percentages of organic compounds (P = 0.0125). All specimens exhibited two crystalline transformations when heated from ambient temperature to 130°C. MC presented the highest percentage of GP. CONCLUSIONS: No correlation was observed between chemical composition and thermal behavior. Each of the products showed thermal behavior that is typical of beta-phase gutta-percha.
RESUMO
This in vivo study investigated the time of degradation of root filling material (trans 1,4-polyisoprene) retrieved from endodontically treated teeth and correlated the occurrence of degradation with the longevity of endodontics. Thirty-six root-filled teeth with different filling times (2 to 30 years) and with and without periapical lesions were selected. All teeth presented clinical indication for root canal retreatment. The association among filling time, presence of periapical lesion and root filling material degradation was investigated. Root filling samples were retrieved from the root canals using a Hedströ m file without solvent. The trans 1,4-polyisoprene was isolated by root filling solubilization in chloroform followed by filtration and centrifugation. GPC and FT-IR were the analytical techniques utilized. Degradation of trans 1,4-polyisoprene occurred with time, as a slow process. It is an oxidative process, and production of carboxyl and hydroxyl groups in the residual polymer were observed. Statistically significant decrease of molar mass was observed after 5 (p=0.0001) and 15 (p=0.01) years in teeth with and without periapical lesion, respectively. Bacteria participated in polymer degradation. Gutta-percha aging was proven an important factor for the long-term success of endodontic treatment. The findings of the present study showed that, after 15 years, polymer weight loss may decrease the capacity of the filling mass to seal the root canal space and prevent re-infection, thus compromising significantly the longevity of root canal therapy.