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1.
Pesqui. vet. bras ; 39(10): 837-842, Oct. 2019. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1056907

RESUMO

Chitosan has been successfully used as a biomaterial with several purposes in many species. In this study, chitosan membranes were produced with six different types of materials, and their behavior were evaluated upon implantation in the subcutaneous tissue of the flank of twelve healthy horses. We assessed chitosan membranes obtained from commercial chitosan, impregnated or not with silver nanoparticles, sterilized with ethylene oxide (CCEO, n=3; CCSNEO, n=3) or by ultraviolet radiation (CCUR, n=3; CCSNUR, n=3), and chitosan membranes obtained from squid gladius, sterilized with ethylene oxide (SCEO, n=6) or by ultraviolet radiation (SCUR, n=6). The same animals were randomly used in two experimental groups, with a minimum interval of 60 days between procedures, respecting the fact of only one flank side, left or right, be under evaluation by experimental period. After preparation of the membranes and implantation in the flank subcutaneous tissue of the horses, macroscopic and ultrasonographic evaluations of the implant regions were performed, as well as physical examination, blood count and fibrinogen measurement. No clinical or laboratory abnormalities were observed. All animals that received commercial chitosan membranes, regardless of the preparation technique, showed rejection to the biomaterials, considering that 100% of the surgical wounds presented dehiscence of suture and expulsion of the implants. The animals that received squid gladius chitosan membranes showed success in the treatment, with healing by primary intention of the surgical wound. We conclude that squid gladius chitosan membranes are biocompatible and biodegradable when implanted in the subcutaneous tissue of the flank of healthy horses.(AU)


A quitosana tem sido utilizada, com sucesso, como biomaterial para diversas espécies e finalidades. Neste estudo foi avaliada a confecção de membranas de quitosana, produzidas a partir de seis tipos de materiais diferentes e foi estudado seu comportamento quando implantadas no tecido subcutâneo do flanco de doze equinos sadios. Foram avaliadas membranas de quitosana obtidas de quitosana comercial, impregnadas ou não com nanopartículas de prata, esterilizadas com óxido de etileno (QCOE, n=3; QCNPOE, n=3) ou por radiação ultravioleta (QCRU, n=3; QCNPRU, n=3) e membranas de quitosana obtidas do gládio de lula, esterilizadas com óxido de etileno (GLOE, n=6) ou por radiação ultravioleta (GLRU, n=6). Os mesmos animais foram utilizados em dois grupos experimentais, de forma aleatória, com um intervalo mínimo de sessenta dias entre os procedimentos, respeitando-se o fato de apenas um lado do flanco, esquerdo ou direito, estar em avaliação por período experimental. Após preparo das membranas e implantação no tecido subcutâneo do flanco dos equinos, foram realizadas avaliações macroscópicas e ultrassonográficas das regiões de implante, além de exames físicos, hemogramas e fibrinogênio. Não foram observadas alterações clínicas e laboratoriais. Todos os animais que receberam membranas de quitosana comercial, independente da técnica de preparo, demonstraram rejeição dos biomateriais, uma vez que 100% das feridas cirúrgicas apresentaram deiscência da sutura e expulsão dos implantes. Os animais que receberam as membranas de quitosana de gladio de lula demonstraram sucesso no tratamento, com cicatrização das feridas cirúrgicas por primeira intenção. Conclui-se que membranas de quitosana de gládio de lula são biocompatíveis e biodegradáveis, quando implantadas no tecido subcutâneo do flanco de equinos sadios.(AU)


Assuntos
Animais , Cicatrização , Quitosana/efeitos adversos , Quitosana/uso terapêutico , Cavalos , Implantes de Medicamento
2.
BMC Musculoskelet Disord ; 20(1): 257, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31138200

RESUMO

BACKGROUND: Different substances are combined to compensate for each other's drawbacks and create an appropriate biomaterial. A novel Polyvinyl alcohol (PVA)/chitosan (CS) porous hydrogel was designed and applied to the treatment of osteochondral defects. METHODS: Hydrogels of various PVA/CS ratios were tested for physiochemical and mechanical properties in addition to cytotoxicity and biocompatibility. The hydrogels with the best PVA/CS ratio were used in the animal study. Osteochondral defects were created at the articular cartilage of 18 rabbits. They were assigned to different groups randomly (n = 6 per group): the osteochondral defect only group (control group), the osteochondral defect treated with hydrogel group (HG group), and the osteochondral defect treated with hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) group (HG-BMSCs group). The cartilage was collected for macro-observation and histological evaluation at 12 weeks after surgery. RESULTS: The Hydrogel with PVA/CS ratio of 6:4 exhibited the best mechanical properties; it also showed stable physical and chemical properties with porosity and over 90% water content. Furthermore, it demonstrated no cytotoxicity and was able to promote cell proliferation. The HG-BMSCs group achieved the best cartilage healing. CONCLUSIONS: The novel PVA/CS porous composite hydrogel could be a good candidate for a tissue engineering material in cartilage repair.


Assuntos
Materiais Biocompatíveis/efeitos adversos , Doenças das Cartilagens/terapia , Hidrogéis/efeitos adversos , Transplante de Células-Tronco Mesenquimais , Tecidos Suporte/efeitos adversos , Animais , Doenças das Cartilagens/patologia , Cartilagem Articular/citologia , Cartilagem Articular/lesões , Cartilagem Articular/fisiologia , Proliferação de Células/efeitos dos fármacos , Quitosana/administração & dosagem , Quitosana/efeitos adversos , Condrogênese/efeitos dos fármacos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Modelos Animais de Doenças , Humanos , Hidrogéis/administração & dosagem , Masculino , Teste de Materiais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/efeitos adversos , Porosidade , Coelhos , Regeneração/efeitos dos fármacos , Testes de Toxicidade , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
3.
Carbohydr Polym ; 216: 213-216, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047059

RESUMO

Oxidized regenerated cellulose has become a major local surgical hemostatic biomaterial because of its ease of use, favorable biocompatibility, bactericidal activity and bioabsorption characteristics. Additional clinical indications of oxidized regenerated cellulose include wound repair and tissue reconstruction. Sometimes, some unusual adverse events are described. Studies report cases of minor postoperative complications as nidus of infection or allergic reaction mainly presenting as acute dermatitis, eczema and sieroma. Also, rare and serious cases of foreign body reaction or impingement on nerve, due to not optimal bioabsorption, are showed in various surgical sites. Thus, on the one hand, patients should be informed by their clinicians of the possibility of these low incidence postoperative complications when considering preparations made of cellulose derivatives; and the clinicians should clearly indicate use of this biomaterial in the surgical procedure report so that radiologists may appropriately interpret any unusual findings potentially associated with this biomaterial use and thus avoid misdiagnosis and undue alarm in the follow-up of patients. On the other hand, the biomedical carbohydrate scientist must consider effective experimental design that substantially addresses the clinical adverse events associated with carbohydrate polymer use. Optimal development of carbohydrates for clinical use depends on excellent clinician/biomedical scientist communication.


Assuntos
Plásticos Biodegradáveis/efeitos adversos , Celulose Oxidada/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Quitosana/efeitos adversos , Hemostáticos/efeitos adversos , Humanos , Hipersensibilidade , Tecidos Suporte/efeitos adversos
4.
J Surg Res ; 239: 269-277, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30884383

RESUMO

BACKGROUND: A novel injectable expanding foam based on hydrophobically modified chitosan (HM-CS) was developed to improve hemostasis during surgeries. HM-CS is an amphiphilic derivative of the natural biopolymer chitosan (CS); HM-CS has been shown to improve the natural hemostatic characteristics of CS, but its internal safety has not been systematically evaluated. The goal of this study was to compare the long-term in vivo safety of HM-CS relative to a commonly used fibrin sealant (FS), TISSEEL (Baxter). METHODS: Sixty-four Sprague-Dawley rats (275-325 g obtained from Charles River Laboratories) were randomly assigned to control (n = 16) or experimental (n = 48) groups. Samples of the test materials (HM-CS [n = 16], CS [n = 16], and FS [n = 16]) applied to a nonlethal liver excision (0.4 ± 0.3 g of the medial lobe) in rats were left inside the abdomen to degrade. Animals were observed daily for signs of morbidity and mortality. Surviving animals were sacrificed at 1 and 6 wk; the explanted injury sites were microscopically assessed. RESULTS: All animals (64/64) survived both the 1- and 6-wk time points without signs of morbidity. Histological examination showed a comparable pattern of degradation for the various test materials. FS remnants and significant adhesions to neighboring tissues were observed at 6 wk. Residual CS and HM-CS were observed at the 6 wk with fatty deposits at the site of injury. Minimal adhesions were observed for CS and HM-CS. CONCLUSIONS: The internal safety observed in the HM-CS test group after abdominal implantation indicates that injectable HM-CS expanding foam may be an appropriate internal use hemostatic candidate.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Quitosana/administração & dosagem , Hemostasia Cirúrgica/métodos , Hemostáticos/administração & dosagem , Animais , Quitosana/efeitos adversos , Quitosana/química , Modelos Animais de Doenças , Adesivo Tecidual de Fibrina/administração & dosagem , Hemostáticos/efeitos adversos , Hemostáticos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fígado/cirurgia , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley
5.
J Colloid Interface Sci ; 543: 114-121, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30782517

RESUMO

Contact lenses (CL) provide visual correction but their use may also induce several adverse effects causative of discomfort and conditions that lead to stop or discontinue their use. Discomfort is mainly caused by insufficient wetting, impairment of the antioxidant defence system and eye infections. The current work reports on a single step sonochemical coating of CL with ZnO nanoparticles (NPs), chitosan (CS) and gallic acid (GA). GA and CS are expected to improve the comfort of CL by imparting respectively antioxidant properties and enhanced wettability, while their combination with ZnO NPs provides the CL with antimicrobial properties. The ternary composite coating presents high antibacterial efficiency (>4.5 logs reduction) against S. aureus causative of CL-related conditions, and maintains good biocompatibility (>72%) with human cell lines. The obtained multi-functionality on the CL did not affect their geometry and refractive properties.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Quitosana/farmacologia , Ácido Gálico/farmacologia , Nanopartículas/química , Óxido de Zinco/farmacologia , Antibacterianos/efeitos adversos , Antibacterianos/química , Antioxidantes/efeitos adversos , Antioxidantes/química , Benzotiazóis/antagonistas & inibidores , Linhagem Celular , Quitosana/efeitos adversos , Quitosana/química , Lentes de Contato/efeitos adversos , Ácido Gálico/efeitos adversos , Ácido Gálico/química , Humanos , Testes de Sensibilidade Microbiana , Nanopartículas/efeitos adversos , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos , Ácidos Sulfônicos/antagonistas & inibidores , Propriedades de Superfície , Óxido de Zinco/efeitos adversos , Óxido de Zinco/química
6.
J Mater Sci Mater Med ; 29(11): 158, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30349982

RESUMO

One of the important routes of drug administration for localized delivery of contraceptives and cervical cancer treatment agents is vaginal canal. Due to the low pH of vagina, a pH-responsive drug delivery system was developed. This hydrogel was synthesized based on a mucoadhesive biopolymer, chitosan (CS), that promotes the interaction between the hydrogel and mucosal surface of the vagina, potentially increasing the residence time of the system. This injectable hydrogel was formed via acid-labile Schiff-base linkages between free amine groups and aldehyde functionalities on modified chitosan. A novel approach was taken to add aldehyde functionalities to chitosan using a two-step reaction. Two types of slow and fast degrading hydrogels were prepared and loaded with iron (II) gluconate dihydrate, a non-hormonal spermicide, and doxorubicin hydrochloride, an anti-cancer drug. The release profiles of these drugs at different pH environments were assessed to determine the pH-dependent release mechanism. Mechanical properties, swell-ability and degradation rate of these matrices were studied. The cross-linking density of the hydrogel as well as pH changes played an important role in the characteristic of these hydrogels. The hydrogels degraded faster in lower pH, while the hydrogel with lower cross-linking density showed longer gelation time and faster degradation rate compared to the gel with higher cross-linking density. In vitro cytotoxicity assessment of these hydrogels in 48 h indicated the non-toxic effect of these hydrogels toward mesenchymal stem cells (MSCs) in the test period.


Assuntos
Quitosana/efeitos adversos , Quitosana/química , Hidrogéis/efeitos adversos , Hidrogéis/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Administração Intravaginal , Animais , Configuração de Carboidratos , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Hidrogéis/síntese química , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Reologia
7.
Diab Vasc Dis Res ; 15(4): 348-351, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29682995

RESUMO

AIM: To evaluate whether a combination of isosorbide dinitrate spray and chitosan gel (10%) topically applied can have additive benefits for management of diabetic foot ulcers. METHODS: In a randomized, placebo-controlled, double-blinded clinical trial, 68 patients were divided into four groups: Group 1: treated with chitosan gel; Group 2: isosorbide dinitrate spray; Group 3: combination of isosorbide dinitrate spray and chitosan gel; Group 4: placebo. RESULTS: Histological analyses showed a significant regeneration in all groups ( p < 0.001). On the final assessment of the ulcer, using the combination was found a wound closure percentage of 71 ± 30, 70 ± 27 using isosorbide dinitrate, 58 ± 30 with chitosan and 50 ± 16 with placebo. The number of patients who achieved complete ulcer closure was six using the combination, four with isosorbide dinitrate, three with chitosan and one with placebo. The progression in the healing process of the ulcer showed marked inmunohistochemical differences of Von Willebrand Factor, desmin, vascular endothelial growth factor-A and α-smooth muscle actin in all groups ( p < 0.001), but without notable differences between them. CONCLUSION: The combination was better than placebo to reduce the dimensions of the ulcer, accelerate healing and increase the number of patients who achieved complete closure of the ulcer, but the combination was not better than chitosan or isosorbide dinitrate used separately.


Assuntos
Quitosana/administração & dosagem , Pé Diabético/tratamento farmacológico , Dinitrato de Isossorbida/administração & dosagem , Pele/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Cutânea , Aerossóis , Bandagens , Biomarcadores/metabolismo , Quitosana/efeitos adversos , Pé Diabético/diagnóstico , Pé Diabético/metabolismo , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Géis , Humanos , Dinitrato de Isossorbida/efeitos adversos , Masculino , México , Pele/metabolismo , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversos
8.
Mol Nutr Food Res ; 62(8): e1700842, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29451712

RESUMO

SCOPE: We performed a pooled analysis with trial sequential analysis (TSA) to evaluate the efficacy and safety of chitosan supplementation on serum lipids in humans. METHODS AND RESULTS: Medline, EMBASE, and CENTRAL databases were queried. Impact was expressed as a weighted mean difference (WMD) and 95% confidence interval (CI). Sensitivity analysis was conducted using the leave-one-out method. Statistical heterogeneity, publication bias, TSA, and subgroup analyses were also assessed. Fourteen trials (21 treatment arms) encompassing 1108 participants were suitable for statistical pooling. Chitosan supplementation significantly improved the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in all patients. The WMDs were -0.20 mmol L-1 (95% CI, -0.35 to -0.05; p = 0.009) for TC, and -0.20 mol L-1 (95% CI, -0.26 to -0.15; p = 0.0001) for LDL-C, respectively. TSA demonstrated that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit providing conclusive evidence for the benefit of chitosan. However, no significant changes were seen with high-density lipoprotein cholesterol (HDL-C) and triglycerides. Our findings were robust after sensitivity analyses, and no serious adverse events were reported with chitosan intake. CONCLUSION: Supplementation with chitosan effectively reduces plasma concentrations of TC and LDL-C. Current evidence indicates daily chitosan supplementation as a candidate for therapeutic lipid management strategies.


Assuntos
Anticolesterolemiantes/uso terapêutico , Quitosana/uso terapêutico , Suplementos Nutricionais , Medicina Baseada em Evidências , Hipercolesterolemia/terapia , Adulto , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Quitosana/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Humanos , Hipercolesterolemia/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Nutrients ; 10(1)2018 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-29324705

RESUMO

Chitosan treatment results in significantly lower serum low density lipoprotein (LDL) cholesterol concentrations. To assess the working mechanisms of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol), corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (Body Mass Index, BMI 31.7, range 28.1-38.9 kg/m²) were studied under chitosan (n = 61) and placebo treatments (n = 55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (p = 0.0252) under chitosan (-8.67 ± 18.18 mg/dL, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dL, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increases in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment were not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption, nor with increases of markers for cholesterol and bile acid synthesis.


Assuntos
Anticolesterolemiantes/uso terapêutico , Quitosana/uso terapêutico , Colesterol/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticolesterolemiantes/efeitos adversos , Ácidos e Sais Biliares/sangue , Biomarcadores/sangue , Quitosana/efeitos adversos , Método Duplo-Cego , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Drug Des Devel Ther ; 12: 67-75, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29343944

RESUMO

Background: Chitosan is a popular dietary fiber often used to reduce dietary fat absorption to control weight and blood lipids. However, its effects on blood pressure (BP) have not been fully elucidated. We evaluated the effects of chitosan administration on systolic blood pressure (SBP) and diastolic blood pressure (DBP) through a pooled analysis of available randomized controlled trials (RCTs). Materials and methods: Electronic searches were conducted in Medline, Cochrane Library, Scopus, and EMBASE to identify relevant human placebo-control RCTs. Trials that reported BP changes from baseline to study endpoint in patients receiving treatment of chitosan were included for analysis. Weighted mean difference (WMD) and 95% CIs were pooled using fixed-effects or random-effects models. Statistical heterogeneity, prespecified subgroup, publication bias, sensitivity analysis, and meta-regression assessments were also tested. Results: Six hundred and seventeen participants from eight trials with 10 arms were included. Overall, chitosan administration did not significantly lower SBP (WMD: -1.41 mmHg, 95% CI: -3.29 to 0.47; P=0.14) and DBP (WMD: -0.61 mmHg, 95% CI: -1.75 to 0.52; P=0.29). However, our subgroup analyses indicated that chitosan consumption significantly reduced DBP in shorter-term (<12 weeks) and higher-dose (>2.4 g/day) arms. Funnel plots or Egger's tests analysis (P=0.36 and 0.43 for SBP and DBP, respectively) demonstrated that there was no significant publication bias in this study. Conclusion: This meta-analysis indicates that chitosan consumption significantly decreases DBP at higher dosage and in shorter-term interventions, while chitosan has no significant effects on SBP. However, these results should be interpreted cautiously because of the limited eligible RCTs included in this meta-analysis; further large-scale, well-designed RCTs on this topic are urgently needed.


Assuntos
Pressão Sanguínea , Quitosana/administração & dosagem , Fibras na Dieta/administração & dosagem , Suplementos Nutricionais , Hipertensão/dietoterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quitosana/efeitos adversos , Diástole , Fibras na Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Medicina Baseada em Evidências , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sístole , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Curr Drug Deliv ; 15(4): 594-600, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28425869

RESUMO

BACKGROUND: Retinal neovascularization (NV) is the leading cause of blindness in the majority of ocular diseases. Several treatment approaches have been developed for retinal NV; of these methods, instillation of nanoparticles into the conjunctival sac has shown potential for retinal NV treatment because it does not cause physical damage and is easy to operate. METHODS: In this study, honokiol-loaded chitosan/sulfobutylether-ß-cyclodextrin nanoparticles (HKCS- NPs) were prepared for ophthalmic drug delivery systems. An inclusion complex of honokiol and sulfobutylether-ß-cyclodextrin was used to incorporated insoluble honokiol into chitosan nanoparticles, which were prepared through ionotropic gelation. RESULTS: HK-CS-NPs featured a spherical surface with a narrow size distribution of polydispersity index less than 0.250, a mean size range of 373-523 nm, a positive surface charge of +19.9 to +24.2 mV, and an entrapment efficiency of 84.92%. In vitro release studies showed an initial burst release phase and a sustained release phase of nanoparticles. Moreover, in vivo study showed that HK-CS-NPs exhibited good ocular tolerability and could improve ophthalmic bioavailability of honokiol. In particular, the maximum concentration of honokiol after administration of HK-CS-NPs was enhanced by 1.65 times compared with that after instillation of the honokiol suspension alone. CONCLUSION: This study proposes HK-CS-NPs as a potential ophthalmic delivery system.


Assuntos
Compostos de Bifenilo/administração & dosagem , Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Lignanas/administração & dosagem , Nanopartículas/química , Administração Oftálmica , Animais , Disponibilidade Biológica , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacocinética , Quitosana/administração & dosagem , Quitosana/efeitos adversos , Liberação Controlada de Fármacos , Olho/efeitos dos fármacos , Olho/metabolismo , Lignanas/efeitos adversos , Lignanas/química , Lignanas/farmacocinética , Nanopartículas/administração & dosagem , Nanopartículas/efeitos adversos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Propriedades de Superfície , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/efeitos adversos , beta-Ciclodextrinas/química
12.
BJU Int ; 121(3): 472-478, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28710845

RESUMO

OBJECTIVE: To evaluate the feasibility and the safety of applying chitosan membrane (ChiMe) on the neurovascular bundles (NVBs) after nerve-sparing robot-assisted radical prostatectomy (NS-RARP). The secondary aim of the study was to report preliminary data and in particular potency recovery data. PATIENTS AND METHODS: This was a single-centre, single-arm prospective study, enrolling all patients with localised prostate cancer scheduled for RARP with five-item version of the International Index of Erectile Function scores of >17, from July 2015 to September 2016. All patients underwent NS-RARP with ChiMe applied on the NVBs. The demographics, perioperative, postoperative and complications data were evaluated. Potency recovery data were evaluated in particular and any sign/symptom of local allergy/intolerance to the ChiMe was recorded and evaluated. RESULTS: In all, 140 patients underwent NS-RARP with ChiMe applied on the NVBs. Applying the ChiMe was easy in almost all the cases, and did not compromise the safety of the procedure. None of the patients reported signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging. CONCLUSION: In our experience, ChiMe applied on the NVBs after NS-RARP was feasible and safe, without compromising the duration, difficulty or complication rate of the 'standard' procedure. No patients had signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging. A comparative cohort would have added value to the study. The present paper was performed before Conformité Européene (CE)-mark achievement.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Quitosana/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/farmacologia , Vasos Sanguíneos , Quitosana/efeitos adversos , Quitosana/farmacologia , Disfunção Erétil/etiologia , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Ereção Peniana/efeitos dos fármacos , Nervos Periféricos , Inibidores da Fosfodiesterase 5/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Prostatectomia/efeitos adversos , Recuperação de Função Fisiológica/efeitos dos fármacos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Tadalafila/uso terapêutico
13.
Sci Rep ; 7(1): 16813, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196703

RESUMO

Chitosan is a natural polymer with applications in agriculture, which causes plasma membrane permeabilisation and induction of intracellular reactive oxygen species (ROS) in plants. Chitosan has been mostly applied in the phylloplane to control plant diseases and to enhance plant defences, but has also been considered for controlling root pests. However, the effect of chitosan on roots is virtually unknown. In this work, we show that chitosan interfered with auxin homeostasis in Arabidopsis roots, promoting a 2-3 fold accumulation of indole acetic acid (IAA). We observed chitosan dose-dependent alterations of auxin synthesis, transport and signalling in Arabidopsis roots. As a consequence, high doses of chitosan reduce WOX5 expression in the root apical meristem and arrest root growth. Chitosan also propitiates accumulation of salicylic (SA) and jasmonic (JA) acids in Arabidopsis roots by induction of genes involved in their biosynthesis and signalling. In addition, high-dose chitosan irrigation of tomato and barley plants also arrests root development. Tomato root apices treated with chitosan showed isodiametric cells respect to rectangular cells in the controls. We found that chitosan causes strong alterations in root cell morphology. Our results highlight the importance of considering chitosan dose during agronomical applications to the rhizosphere.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/efeitos dos fármacos , Quitosana/efeitos adversos , Regulação para Baixo , Proteínas de Homeodomínio/genética , Ácidos Indolacéticos/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Quitosana/farmacologia , Ciclopentanos/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Hordeum/efeitos dos fármacos , Hordeum/genética , Hordeum/crescimento & desenvolvimento , Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/genética , Lycopersicon esculentum/crescimento & desenvolvimento , Oxilipinas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Ácido Salicílico/metabolismo
14.
Acta Biomater ; 63: 96-109, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28919508

RESUMO

Anticancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals provided by antigen-presenting cells (APCs). However, it is described that immature dendritic cells (DCs) and macrophages at the tumor site may have an immunosuppressive profile, which limits the activity of effector T cells and supports tumor progression. Therapeutic targeting of these innate immune cells, either aiming at their elimination or re-polarization towards an immunostimulatory profile, has been pointed as an attractive approach to control tumor progression. In the present work, we assessed the potential of Chitosan (Ch)/Poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) to modulate macrophages and DCs inflammatory profile and to impair their ability to promote cancer cell invasion. Interestingly, Ch/γ-PGA NPs, prepared by co-acervation method, induced an immunostimulatory DCs phenotype, enhancing the expression of the co-stimulatory molecules CD86, CD40 and HLA-DR, and the secretion of the pro-inflammatory cytokines TNF-α, IL-12p40 and IL-6. Furthermore, Ch/γ-PGA NPs re-educated IL-10-stimulated macrophages towards a pro-inflammatory profile, decreasing the expression of CD163 and promoting the secretion of IL-12p40 and TNF-α. These alterations in the immune cells phenotype promoted CD4+ and CD8+ T cell activation/proliferation and partially inhibited APCs' ability to induce colorectal cancer cell invasion. Overall, our findings open new perspectives on the use of Ch/γ-PGA NPs as an immunomodulatory therapy for antigen-presenting cells reprogramming, providing a new tool for anticancer therapies. STATEMENT OF SIGNIFICANCE: The immune system is responsible to detect and destroy abnormal cells preventing the development of cancer. However, the immunosuppressive tumor microenvironment can compromise the immune response favoring tumor progression. Thus, immune system modulation towards an immunostimulatory profile can improve anticancer therapies. This research focus on the development of chitosan/poly(γ-glutamic acid) nanoparticles (NPs) to modulate human antigen-presenting cells (APCs) phenotype and to counteract their pro-invasive capacity. Interestingly, Ch/γ-PGA NPs had a prominent effect in inducing macrophages and dendritic cells immunostimulatory phenotype, thus favoring T cell proliferation and inhibiting colorectal cancer cell invasion. We propose that their combination with other immunomodulatory drugs or conventional anticancer therapies can improve patients' outcome.


Assuntos
Células Apresentadoras de Antígenos/patologia , Movimento Celular , Quitosana/efeitos adversos , Inflamação/patologia , Nanopartículas/efeitos adversos , Ácido Poliglutâmico/análogos & derivados , Células Apresentadoras de Antígenos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Endocitose/efeitos dos fármacos , Humanos , Interleucina-10/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Invasividade Neoplásica , Tamanho da Partícula , Fenótipo , Ácido Poliglutâmico/administração & dosagem , Ácido Poliglutâmico/efeitos adversos , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos
15.
Harmful Algae ; 65: 27-39, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28526117

RESUMO

We tested the hypothesis that a combination of coagulant and ballast could be efficient for removal of positively buoyant harmful cyanobacteria in shallow tropical waterbodies, and will not promote the release of cyanotoxins. This laboratory study examined the efficacy of coagulants [polyaluminium chloride (PAC) and chitosan (made of shrimp shells)] alone, and combined with ballast (lanthanum modified bentonite, red soil or gravel) to remove the natural populations of cyanobacteria collected from a shallow eutrophic urban reservoir with alternating blooms of Cylindrospermopsis and Microcystis. PAC combined with ballast was effective in settling blooms dominated by Microcystis or Cylindrospermopsis. Contrary to our expectation, chitosan combined with ballast was only effective in settling Cylindrospermopsis-dominated blooms at low pH, whereas at pH≥8 no effective flocculation and settling could be evoked. Chitosan also had a detrimental effect on Cylindrospermopsis causing the release of saxitoxins. In contrast, no detrimental effect on Microcystis was observed and all coagulant-ballast treatments were effective in not only settling the Microcystis dominated bloom, but also lowering dissolved microcystin concentrations. Our data show that the best procedure for biomass reduction also depends on the dominant species.


Assuntos
Hidróxido de Alumínio/farmacologia , Bentonita/farmacologia , Quitosana/farmacologia , Coagulantes/farmacologia , Cylindrospermopsis/efeitos dos fármacos , Microcystis/efeitos dos fármacos , Biomassa , Quitosana/efeitos adversos , Cylindrospermopsis/crescimento & desenvolvimento , Proliferação Nociva de Algas/efeitos dos fármacos , Microcistinas/metabolismo , Microcystis/crescimento & desenvolvimento , Saxitoxina/metabolismo , Solo/química
16.
J Vasc Access ; 18(3): 220-224, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28478622

RESUMO

BACKGROUND: Patients on chronic hemodialysis often have acquired coagulopathy that can aggravate bleeding from puncture site after needle extraction. Chitosan-based pads have been reported to accelerate hemostasis even in the presence of coagulopathy. The aim of this study was to evaluate the hemostatic efficacy of the chitosan pads compared to gauze pads, applied for local hemostasis. METHODS: A crossover study in a cohort of patients on hemodialysis with extended time to hemostasis after needle extraction. At the end of each dialysis, either gauze or chitosan pad was applied on both access points (arterial and venous). The type of pad was changed in the next dialysis all together 5 times in each patient (10 applications per patient for every pad). RESULTS: A total of 288 applications, 144 for each type of pad, were performed in 15 patients. The average time to hemostasis for the entire group was significantly shorter with the chitosan pads compared to the regular gauze pads ("arterial" point 3 vs. 18.5 min, p<0.001 "venous" access 2.8 vs. 13.2 min, p<0.001, respectively). CONCLUSIONS: Chitosan pads significantly reduce time to hemostasis and should be considered for the treatment of accessible bleeds in patients with coagulopathy.


Assuntos
Quitosana/administração & dosagem , Hemorragia/prevenção & controle , Técnicas Hemostáticas , Hemostáticos/administração & dosagem , Punções/efeitos adversos , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Bandagens , Quitosana/efeitos adversos , Estudos Cross-Over , Feminino , Hemorragia/etiologia , Técnicas Hemostáticas/efeitos adversos , Hemostáticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
17.
J Ocul Pharmacol Ther ; 33(5): 375-382, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28441068

RESUMO

PURPOSE: This study was designed to evaluate the effect of chitosan-N-acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with dry eye syndrome (DES). METHODS: This was a controlled, randomized, double-blind clinical investigation with patients assigned to 2 cohorts. In Cohort I, 21 patients were randomized to receive 1 instillation of C-NAC eye drops in 1 eye and placebo (normal saline solution) in the contralateral eye. In Cohort II, 17 patients were randomized to receive C-NAC eye drops once (QD) or twice (BID) daily for 5 days. TFT was assessed with a custom-built ultrahigh-resolution optical coherence tomography system. RESULTS: In Cohort I, mean TFT increased from 3.9 ± 0.5 µm predose to 4.8 ± 1.1 µm 10 min postdose after treatment with C-NAC. The increase was significantly different from placebo over time (P < 0.0001) and remained stable until 24 h postdose. In Cohort II, TFT increased with QD and BID instillation, with no significant difference between regimens. In both groups, Ocular Surface Disease Index scores improved, fewer patients presented with corneal damage, and symptoms of ocular discomfort/conjunctival redness were reduced. CONCLUSIONS: A single instillation of C-NAC significantly increased mean TFT in patients with DES as early as 10 min after instillation and lasted for 24 h. The magnitude of the increase in TFT following a single instillation was comparable with that after instillation twice daily over 5 days. Corneal damage improved in >60% of patients. C-NAC could be a viable treatment option for DES.


Assuntos
Acetilcisteína/efeitos adversos , Acetilcisteína/uso terapêutico , Quitosana/análogos & derivados , Síndromes do Olho Seco/tratamento farmacológico , Acetilcisteína/administração & dosagem , Adulto , Quitosana/administração & dosagem , Quitosana/efeitos adversos , Quitosana/uso terapêutico , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Masculino , Lágrimas/química , Lágrimas/metabolismo , Tomografia de Coerência Óptica
18.
Drug Deliv ; 24(1): 459-466, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28219253

RESUMO

A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quitosana/análogos & derivados , Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Fluoruracila/análogos & derivados , Fluoruracila/administração & dosagem , Nanopartículas/química , Pró-Fármacos/administração & dosagem , Células A549 , Absorção Fisiológica , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Quitosana/efeitos adversos , Quitosana/farmacocinética , Quitosana/farmacologia , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Fluoruracila/farmacologia , Glicosilação , Meia-Vida , Hemólise/efeitos dos fármacos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Camundongos , Nanopartículas/efeitos adversos , Nanopartículas/ultraestrutura , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Coelhos , Distribuição Aleatória , Ratos Sprague-Dawley , Distribuição Tecidual
19.
Artif Cells Nanomed Biotechnol ; 45(6): 1-8, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27362580

RESUMO

Based on our previous work on the PLGA nanoparticles modified with biotinylated chitosan (Bio-CS-PLGA NPs), we further studied the stability, toxicity, pharmacokinetics, and in vivo efficacy. The safety of NPs was studied through single-dose toxicity test in mice, and the result showed that NPs were well tolerated at the dose of 300 mg/kg. Compared with the free EPB group, the NPs group exhibited higher plasma drug concentration, longer half-life time. EPB-loaded NPs significantly inhibited the tumor growth compared to free EPB. All results suggested that Bio-CS-PLGA NPs were stable, safe, and showed a promising potential on targeted drug delivery.


Assuntos
Quitosana , Sistemas de Liberação de Medicamentos/métodos , Ácido Láctico , Neoplasias Experimentais/tratamento farmacológico , Ácido Poliglicólico , Animais , Biotinilação , Quitosana/efeitos adversos , Quitosana/farmacocinética , Quitosana/farmacologia , Feminino , Ácido Láctico/efeitos adversos , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Camundongos , Ácido Poliglicólico/efeitos adversos , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Wistar
20.
Drug Chem Toxicol ; 40(4): 375-382, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27866417

RESUMO

Recently, development of fluorescent nanoparticle-based probes for various bioimaging applications has attracted great attention. This work aims to develop a new type fluorescent nanoparticle conjugate and evaluate its cytotoxic effects on A549 and BEAS 2B cell lines. Throughout the study, ionically crosslinked chitosan nanoparticles (CNs) were conjugated with carboxylated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY-COOH). The results of conjugates (BODIPY-CNs) were investigated with regard to their physic-chemical, optical, cytotoxic properties and cellular internalization. The morphology of BODIPY-CNs was found to be spherical in shape and quite uniform having average diameter of 70.25 ± 11.99 nm. Cytotoxicty studies indicated that although BODIPY-COOH itself was quite toxic on both A549- and BEAS 2B-treated cells, CNs increased the cell viability of both cell lines via conjugation to BODIPY-COOH fluorescent molecule up to 67% for A549 and 74% for BEAS 2B cells. These results may suggest a possible utilization of the new fluorescent nanoparticle-based probe for bioimaging in biology and medicine.


Assuntos
Brônquios/metabolismo , Quitosana/metabolismo , Corantes Fluorescentes/metabolismo , Nanopartículas/metabolismo , Porfobilinogênio/análogos & derivados , Mucosa Respiratória/metabolismo , Absorção Fisiológica , Brônquios/citologia , Brônquios/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/efeitos adversos , Quitosana/química , Diagnóstico por Imagem/efeitos adversos , Difusão Dinâmica da Luz , Corantes Fluorescentes/efeitos adversos , Corantes Fluorescentes/química , Humanos , Microscopia de Força Atômica , Microscopia Confocal , Microscopia Eletrônica de Varredura , Nanopartículas/efeitos adversos , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Porfobilinogênio/efeitos adversos , Porfobilinogênio/química , Porfobilinogênio/metabolismo , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier
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