Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 363
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
J Agric Food Chem ; 68(1): 358-368, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31815446

RESUMO

Nanoscale chitosan materials exhibit size-specific properties that make them useful in agri-food and biomedical applications. Chitosan nanoparticles (Chnps) are being explored as nanocarrier platforms to increase oral bioavailability of drugs and nutraceuticals, but little is known of their fate and transformations in the gastrointestinal tract (GIT) or of their potential toxicity. Here, the GIT fate and cytotoxicity of Chnps, soluble starch-coated Chnps (SS-Chnps), and bulk chitosan powder (Chp), were assessed using a 3-phase simulated digestion and an in vitro cellular small intestinal epithelium model. Physico-chemical characterization revealed dissolution of Chp, but not of Chnps or SS-Chnps, during the gastric phase of digestion, stability of the starch coating of SS-Chnps in the oral and gastric phases, and agglomeration of all materials during the small intestinal phase. A slight but significant (10%, p < 0.01) increase in cytotoxicity (LDH release) was observed with exposure to digested Chnps but not Chp or SS-Chnps.


Assuntos
Quitosana/química , Quitosana/metabolismo , Epitélio/metabolismo , Intestino Delgado/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Disponibilidade Biológica , Células CACO-2 , Quitosana/toxicidade , Trato Gastrointestinal/metabolismo , Humanos , Cinética , Modelos Biológicos , Nanopartículas/toxicidade , Tamanho da Partícula
2.
J Sci Food Agric ; 100(2): 794-802, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31612484

RESUMO

BACKGROUND: Low-sodium sausages were manufactured using sodium substitution and biopolymer encapsulation. A diet comprising 10% treatment sausages (six treatment groups: C (100% NaCl), T1 (55% sodium substitute + 45% saltwort salt), T2 (55% sodium substitute + 45% saltwort salt with chitosan), T3 (55% sodium substitute + 45% saltwort salt with cellulose), T4 (55% sodium substitute + 45% saltwort salt with dextrin), and T5 (55% sodium substitute + 45% saltwort salt with pectin)) was added to a 90% commercial mouse diet for 4 weeks. RESULTS: Subacute toxicity, hematology, liver function, and organ weight tests in low-sodium sausage groups showed results similar to those of the control group, and all toxicity test levels were within normal ranges. CONCLUSIONS: All low-sodium sausage types tested are suggested to be safe in terms of subacute toxicity. Moreover, low-sodium sausages can be manufactured by biopolymer encapsulation of saltwort using pectin, chitosan, cellulose, and dextrin without toxicity. © 2019 Society of Chemical Industry.


Assuntos
Biopolímeros/análise , Aditivos Alimentares/análise , Manipulação de Alimentos/métodos , Produtos da Carne/análise , Salsola/química , Sódio/análise , Animais , Biopolímeros/metabolismo , Biopolímeros/toxicidade , Celulose/análise , Celulose/metabolismo , Celulose/toxicidade , Quitosana/análise , Quitosana/metabolismo , Quitosana/toxicidade , Feminino , Aditivos Alimentares/metabolismo , Aditivos Alimentares/toxicidade , Manipulação de Alimentos/instrumentação , Masculino , Produtos da Carne/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Salsola/metabolismo , Salsola/toxicidade , Sódio/metabolismo , Sódio/toxicidade , Suínos
3.
Carbohydr Polym ; 229: 115498, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826492

RESUMO

Controlled release and tumor-selective distribution are highly desirable for anticancer nanomedicines. Here, we design and synthesize an anisamide-conjugated N-octyl-N,O-maleoyl-O-phosphoryl chitosan (a-OMPC) which can form amphiphilic micelles featuring pH-responsive release and high affinity to sigma-1 receptor-overexpressed tumors for paclitaxel (PTX) delivery. Thereinto, maleoyl and phosphoryl groups cooperatively contribute to pH-responsive drug release due to a conversion from hydrophile to hydrophobe in the acidic microenvironment of endo/lysosomes. We demonstrated that PTX-loaded a-OMPC micelles (PTX-aM) enhanced the cellular internalization via the affinity between anisamide and sigma-1 receptor, rapidly released drug in endo/lysosomes and elevated the cytotoxicity against PC-3 cells. The in vivo studies further verified that PTX-aM could largely accumulate at the tumor site even after 24 h of administration, resulting in obvious inhibition effect and prolonged survival period in PC-3 tumor xenograft-bearing mice. Moreover, OMPC showed no obvious hemolytic and acute toxicity. Collectively, this chitosan derivate holds a promising potential in application of prostate cancer-targeted drug delivery system.


Assuntos
Quitosana/química , Interações Hidrofóbicas e Hidrofílicas , Terapia de Alvo Molecular , Paclitaxel/química , Paclitaxel/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Receptores sigma/metabolismo , Animais , Quitosana/toxicidade , Preparações de Ação Retardada , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Regulação Neoplásica da Expressão Gênica , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Teste de Materiais , Camundongos , Micelas , Células PC-3 , Paclitaxel/uso terapêutico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Exp Eye Res ; 188: 107805, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31526807

RESUMO

Macular edema (ME), which is present in various retinal diseases, leads to permanent retinal structural damage and threatens vision. The intravitreal/periocular injection of triamcinolone acetonide (TA) can improve the prognosis of ME; however, further exploration of noninvasive delivery systems is essential. Therefore, as a continuation of our previous study using TA-chitosan coated liposomes (TA-CHLs) as a topical drug delivery system, the present study aimed to determine the drug safety, stability, permeability, and bioavailability of TA-CHLs. The study was based on detecting the delivery of a fluorescent dye to the retina using optical coherence tomography angiography in rats. Marked cellular uptake was observed in cell lines. TA-CHL toxicity was investigated in cell culture. Clinical ocular safety was evaluated by measuring the corneal thickness and intraocular pressure. In preclinical studies on a laser-induced retinal edema rat model, the TA-CHL eye drops had dramatic therapeutic effect in remission of retinal edema over 10 days. These results demonstrated that TA-CHL was nontoxic and had good bioavailability in vitro and in vivo. The results of the present study indicated that this formulation could be an effective therapeutic approach and the TA-CHL eye drops may represent a new option for retinal diseases.


Assuntos
Quitosana/uso terapêutico , Materiais Revestidos Biocompatíveis , Glucocorticoides/uso terapêutico , Lipossomos , Papiledema/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Administração Oftálmica , Animais , Disponibilidade Biológica , Barreira Hematorretiniana/efeitos dos fármacos , Quitosana/farmacocinética , Quitosana/toxicidade , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Feminino , Corantes Fluorescentes/metabolismo , Glucocorticoides/farmacocinética , Glucocorticoides/toxicidade , Pressão Intraocular/efeitos dos fármacos , Injeções Intravítreas , Soluções Oftálmicas , Papiledema/fisiopatologia , Ratos , Ratos Endogâmicos BN , Tomografia de Coerência Óptica , Triancinolona Acetonida/farmacocinética , Triancinolona Acetonida/toxicidade , Acuidade Visual/efeitos dos fármacos
5.
Carbohydr Polym ; 223: 115061, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31426963

RESUMO

In this study, chitosan oligosaccharide (COS)-vanillin imine (COS-Vani Imine)-based dual pH responsive nano-micelles (DPRNs) were synthesized. The resultant DPRNs were used for encapsulating genistein and its ultimate release upon pH change. The overall concept of DPRNs for the targeted delivery of hydrophobic anticancer drugs was successfully demonstrated. The DPRNs were spherical in shape, nanoscale in dimension (71.2-163.4 nm), with dual pH response. The encapsulation/loading of genistein into DPRNs was achieved and the resultant genistein-loaded DPRNs were stable under the physiological pH (˜7.4); under the cancer cell extracellular pH (˜6.8), the amino groups in COS is protonated, thus becoming positively charged, facilitating their adsorption onto negatively charged cancer cells. Under the cancer cell intracellular pH (˜5.0), the genistein-loaded DPRNs were destroyed as a result of the cleavage of pH sensitive benzoic imine, thereby releasing the loaded genistein.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Micelas , Nanoestruturas/química , Oligossacarídeos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quitosana/síntese química , Quitosana/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Genisteína/química , Genisteína/farmacologia , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nanoestruturas/toxicidade , Oligossacarídeos/síntese química , Oligossacarídeos/toxicidade
6.
Food Chem ; 301: 125247, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377626

RESUMO

In this work, we developed a simple method for the preparation of N-(3-azido-2-hydroxypropyl)chitosan. We compared the antibacterial activity of N-(3-azido-2-hydroxypropyl)chitosans and previously synthesized N-(2-azidoethyl)chitosans. N-(3-azido-2-hydroxypropyl)chitosans possess higher antibacterial effect which is comparable with that of ampicillin and gentamicin. The effect is due to azido pharmacophore -CH2-CH(OH)-CH2-N3 (for N-(3-azido-2-hydroxypropyl)chitosan) or -CH2-CH2-N3 (for N-(2-azidoethyl)chitosan) introduced in chitosan chain, since the corresponding organic azides NH2-CH2-CH2-N3 and NH2-CH2-CH2-N3 are characterized by high antibacterial activity. However, high antibacterial organic azides NH2-CH2-CH2-N3 and NH2-CH2-CH2-N3 are characterized by high toxicity. Their conjugation to the chitosan chain saves their antibacterial effect, but strongly diminishes their toxicity, and the toxicity of the resulting derivatives is comparable with that of the starting chitosan. These findings are of interest to food science, since novel effective food coatings can be developed on basis of prepared derivatives.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Azidas/química , Quitosana/química , Quitosana/farmacologia , Embalagem de Alimentos , Antibacterianos/toxicidade , Quitosana/toxicidade
7.
Carbohydr Polym ; 222: 115002, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320044

RESUMO

Chitosan has become promising as a biomaterial because of its biocompatible, biodegradable nature and non-toxic. The biochemical and antioxidant properties of chitosan modified with acetylacetone and ethylenediamine (Cacen) or diethylenetriamine (Cacdien) associated with ceftazidime (F) were investigated. Chitosan was characterized using Elemental Analysis (CHN), Thermal Analysis (TG/DTG/DSC), X-Ray Diffractometry (XRD), and was investigated an in vitro hemolytic cytotoxicity test, Artemia saline larvae for toxicity and in vitro antioxidant activity by DPPH (2,2-diphenyl-1-picrylhydrazyl). The chemical modification was confirmed by CHN, XRD and TG. The Cacen, Cacdien, CacenF and CacdienF derivatives presented high percentages of nitrogen (7.6%, 7.9%, 14.1% and 19.2%, respectively), confirming the modification and drug adsorption. The average molecular weight of chitosan and its derivatives were 132 kDa, with very few variations after modification. This incorporation decreased in the crystallinity index of Cacen (7.1%) and Cacdien (4.3%), as well as the incorporation of the drug (CacenF 0.3% and CacdienF 3.4%). FTIR spectra showed bands at 1580-1654 cm-1 referring to carbonyl and imine group and bands at 3500-3300 and 1462-1264 cm-1 related to vibration and deformation the amine group. 13C NMR spectroscopy was observed new peaks in carbonyl and imine regions (170-200 ppm). The thermal stability of the derivatives without the drug improved according to TG/DTG/DSC analysis, however there were decreased in the derivatives with the drug. The biocompatibility of the derivatives was confirmed by the low hemolytic rate (<5%), non-toxic on Artemia salina (LD50%>3000 ppm), and significant index (1-34%) of antioxidant activity. The results demonstrated that chitosan and its derivatives are promising biomaterials.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Materiais Biocompatíveis/farmacologia , Ceftazidima/farmacologia , Quitosana/análogos & derivados , Quitosana/farmacologia , Adsorção , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Antioxidantes/química , Antioxidantes/toxicidade , Artemia/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Ceftazidima/química , Ceftazidima/toxicidade , Quitosana/toxicidade , Cães , Hemólise/efeitos dos fármacos
8.
Carbohydr Polym ; 222: 115007, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320087

RESUMO

Polymeric films with enhanced mechanical performance were fabricated by incorporation of bone ash (BA) at various concentrations (0-25 v. %) into chitosan/gelatin (CTS/GEL) polymeric structure as a wound healing-dressing. The test results for mechanical performance of polymeric films proved that the encapsulation of BA into the polymeric films enhances the elastic modulus and tensile strength of polymeric films significantly. Oxygen permeability and water vapor transmission rate (WVTR) of films were also improved by BA reinforcement. Ciprofloxacin was chosen as the antibacterial model drug. The release of ciprofloxacin was provided in a more controlled manner at pH 7.4 owing to the incorporation of bone ash into the polymeric films. Also, drug loaded films showed great antibacterial activity against Escherichia coli and Bacillus subtilis bacteria. The results prove that ciprofloxacin loaded BA reinforced CTS/GEL composite films are potentially applicable in controlled drug delivery as wound dressings.


Assuntos
Antibacterianos/farmacologia , Bandagens , Quitosana/química , Ciprofloxacino/farmacologia , Gelatina/química , Minerais/química , Animais , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular , Quitosana/toxicidade , Liberação Controlada de Fármacos , Módulo de Elasticidade , Escherichia coli/efeitos dos fármacos , Gelatina/toxicidade , Camundongos , Testes de Sensibilidade Microbiana , Minerais/toxicidade , Oxigênio/química , Permeabilidade , Resistência à Tração
9.
Int J Biol Macromol ; 137: 495-503, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31276722

RESUMO

Physically cross-linked double-network (DN) hydrogels are capturing more and more attention due to their good mechanical properties and self-recovery ability. However, they usually suffer from complicated preparation process and fussy performance regulation, which severely limit their applications in many fields. Herein, we fabricated a physically cross-linked poly(vinyl alcohol)-(2-hydroxypropyltrimethyl ammonium chloride chitosan) (PVA-HACC) DN hydrogels without organic solvents or toxic cross-linking agents via a simple two-step method of freezing/thawing and immersion processing. The effects of immersion time and concentration of Na3Cit solution on the structures and mechanical properties of the hydrogels were investigated. The obtained hydrogels exhibited excellent mechanical properties including high elastic modulus (1.44 MPa), high strength (a maximal tensile fracture stresses of 4.14 MPa and a maximal compressive stresses of over 70 MPa at 98% strain), and superior fracture toughness (17.09 MJ/m3). In addition, good self-recovered property and anti-fatigue performance were realized for the hydrogels owing to the reversible HACC ionic networks. The preparation of PVA-HACC DN hydrogels offers a new guidance for the design and synthesis of environmentally friendly DN hydrogels with outstanding mechanical properties and broad application prospects.


Assuntos
Quitosana/química , Hidrogéis/química , Fenômenos Mecânicos , Células 3T3 , Animais , Sobrevivência Celular/efeitos dos fármacos , Quitosana/análogos & derivados , Quitosana/toxicidade , Teste de Materiais , Camundongos , Álcool de Polivinil/química , Compostos de Amônio Quaternário/química , Água/química
10.
Carbohydr Polym ; 220: 22-29, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31196544

RESUMO

The control of chitosan/silver nanoparticle composite microsphere (CAgMs) size is crucial for tuning its function. In the current work, monodisperse organically-modified CAgMs with controllable size were synthesized using a two-step method. The fine-tuning of the microsphere size was confirmed by many reaction parameters while the cross-linking agent was the key research object. Through physical and thermodynamic analysis, we found the cross-linking agent-induced smaller size, higher silver concentration, more heightened glass transition temperature and stronger hydrogen bond network. The as-prepared microspheres exhibited strong bacteriostasis and fresh-keeping function depending on cross-linking agent concentration. The phenomenon is believed to be derived from the difference in microorganism adsorption and killing ability from induced varying specific surface area and encapsulated silver content. Our current work highlights the size-controllable preparation of CAgMs, and based on our findings, small size CAgMs can be a promising candidate in the field of antibacterial and fruit preservation applications.


Assuntos
Antibacterianos/farmacologia , Quitosana/toxicidade , Conservação de Alimentos/métodos , Malpighiaceae/microbiologia , Nanopartículas Metálicas/toxicidade , Microesferas , Prata/toxicidade , Quitosana/química , Escherichia coli/efeitos dos fármacos , Nanopartículas Metálicas/química , Tamanho da Partícula , Penicillium/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos
11.
Carbohydr Polym ; 221: 1-9, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31227147

RESUMO

Chitosan samples from two mushroom species (Boletus bovinus, Laccaria laccata) were obtained and characterized by viscosimetry, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), elemental analyses (EA), nuclear magnetic resonance spectroscopy (13C NMR), X-ray diffraction (XRD) and thermogravimetric (TGA) analyses. Properties of the fungal chitosan samples were compared to commercial low-molecular weight chitosan, crustacean chitosan (Cervimunida johni) and chitosan obtained from an insect (Hilobius abietis). Additionally, the cytotoxic properties of chitosan in vitro on cancerous hepatoma and non-cancerous ovary cells cultivated on films with different chitosan concentrations was evaluated. As a conclusion, this study clearly revealed that low-molecular weight chitosan films and solutions with high degree of deacetylation can act cytotoxically on both tumor MH-22A and normal CHO cells in vitro. Consequently, this work may be useful for further investigations of natural anticancer products in medical areas.


Assuntos
Antineoplásicos/farmacologia , Quitosana/farmacologia , Laccaria/química , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Células CHO , Linhagem Celular Tumoral , Quitosana/química , Quitosana/toxicidade , Cricetulus , Camundongos , Peso Molecular , Necrose/induzido quimicamente
12.
Carbohydr Polym ; 221: 84-93, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31227170

RESUMO

In this study, we report a novel pH and temperature responsive paclitaxel-loaded drug delivery system based on chitosan and di(ethylene glycol) methyl ether methacrylate. This was functionalized with hyaluronic acid to permit active targeting of CD44-overexpressing human breast cancer cells. The resultant HA-CS-g-PDEGMA-PTX nanoparticles (NPs) have small and uniform sizes (˜170 nm), a high drug loading (13.6 ±â€¯1.3%) and high encapsulation efficiency (76.2 ±â€¯8.5%). Cell viability and confocal microscopy experiments demonstrated that the NPs could effectively target and kill MDA-MB-231 human breast cancer cells, but were much less toxic to healthy human umbilical vein endothelial cells. In vivo biodistribution studies in mice showed that the NPs accumulated in the tumor site, while free drug was distributed more widely and rapidly cleared from the body. Histopathological studies revealed that the NPs led to enhanced apoptosis in the tumor site, which resulted in reduced tumor growth. The NPs prepared in this work have great potential for the treatment of breast cancers, and further offer a platform with which to target other cancers.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Quitosana/síntese química , Quitosana/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Etilenoglicóis/síntese química , Etilenoglicóis/química , Etilenoglicóis/toxicidade , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Ácido Hialurônico/toxicidade , Metacrilatos/síntese química , Metacrilatos/química , Metacrilatos/toxicidade , Camundongos , Nanopartículas/toxicidade , Paclitaxel/farmacologia , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Int J Biol Macromol ; 136: 823-830, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31228504

RESUMO

Chitosan as a biopolymer is an attractive vehicle for biomedical applications due to its unique characteristics. In order to improve chitosan's physicochemical features, chemical modification has been carried out to make it more suitable for such approaches. The aim of this study was to prepare and evaluate thiolated chitosan-lauric acid as a new chitosan derivative for biomedical use. Lauric acid was introduced to chitosan via stable amide bond between carboxylic acid group of fatty acid and the amine in the chitosan and thiolation was carried out using thioglycolic acid. Resulted polymers were characterized by FTIR, 1H NMR and TGA. Moreover, cell viability assessment of new derivative was performed using MTT method. FTIR and 1H NMR results showed that both substitution reactions were successfully completed. Furthermore, new synthesized polymer had no significant cytotoxicity against normal gingiva human cells (HGF1-PI 1).These findings confirm that this new derivative can be introduced as a suitable polymer for biomedical purposes such as mucosal drug delivery.


Assuntos
Quitosana/síntese química , Quitosana/toxicidade , Citotoxinas/síntese química , Citotoxinas/toxicidade , Ácidos Láuricos/química , Compostos de Sulfidrila/química , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Quitosana/química , Citotoxinas/química , Relação Dose-Resposta a Droga , Gengiva/citologia , Humanos , Interações Hidrofóbicas e Hidrofílicas
14.
Carbohydr Polym ; 216: 1-16, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047045

RESUMO

Sinapic acid (SA) is a plant-derived phenolic compound known for its multiple biological properties, but its role in the promotion of bone formation is not yet well-studied. Moreover, the delivery of SA is hindered by its complex hydrophobic nature, limiting its bioavailability. In this study, we fabricated a drug delivery system using chitosan nanoparticles (nCS) loaded with SA at different concentrations. These were incorporated into polycaprolactone (PCL) fibers via an electrospinning method. nCS loaded with 50 µM SA in PCL fibers promoted osteoblast differentiation. Furthermore, SA treatment activated the osteogenesis signaling pathways in mouse mesenchymal stem cells. A critical-sized rat calvarial bone defect model system identified that the inclusion of SA into PCL/nCS fibers accelerated bone formation. Collectively, these data suggest that SA promoted osteoblast differentiation in vitro and bone formation in vivo, possibly by activating the TGF-ß1/BMP/Smads/Runx2 signaling pathways, suggesting SA might have therapeutic benefits in bone regeneration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Quitosana/química , Ácidos Cumáricos/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Poliésteres/química , Animais , Diferenciação Celular/efeitos dos fármacos , Quitosana/toxicidade , Ácidos Cumáricos/toxicidade , Portadores de Fármacos/toxicidade , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Nanopartículas/toxicidade , Osteogênese/efeitos dos fármacos , Poliésteres/toxicidade , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Crânio/efeitos dos fármacos , Crânio/patologia , Resistência à Tração
15.
Carbohydr Polym ; 216: 332-342, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047074

RESUMO

Chitosan has received a lot of attention as a carrier for small interfering RNA (siRNA), due to its capacity for complexation and intracellular release of these molecules. However, one of its limitations is its insolubility at neutral pH and the tendency towards aggregation of its nanoparticles in isotonic ionic strength. In this study, a series of amphipathic chitosans were synthesized by varying the degree of acetylation (DA) from ˜2 to ˜30 mol% and the degree of substitution (DS) from 5 to 25%. by tertiary amino groups (DEAE) The results showed that the adjustment of these parameters decreases the interparticle interactions mediated by hydrogen bonding to obtain nanoparticles with improved colloidal stability. siRNA-containing nanoparticles of 100 to 150 nm with low polydispersities (0.15-0.2) and slightly positive zeta potentials (˜+ 5 mV) were resistant to aggregation at pH 7.4 and ionic strength of 150 mM. This resistance to aggregation is provided by changes on the nanoparticle surface and highlights the importance of more organized self-assembly in providing colloidal stability at physiological conditions. Additionally, the PEGylation of the most promising vectors conferred favorable physicochemical properties to nanoparticles. The chitosans and their nanoparticles exhibited low toxicity and an efficient cell uptake, as probed by confocal microscopy of rhodamine labeled vectors. The results provide a new approach to overcome the limited stability of chitosan nanoparticles at physiological conditions and show the potential of these amphipathic chitosans as siRNA carriers.


Assuntos
Quitosana/análogos & derivados , Portadores de Fármacos/química , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , Tensoativos/química , Anidridos Acéticos/química , Acetilação , Animais , Quitosana/síntese química , Quitosana/metabolismo , Quitosana/toxicidade , Dietilaminas/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Fluorescência , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Camundongos , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polietilenoglicóis/toxicidade , Células RAW 264.7 , RNA Interferente Pequeno/química , Rodaminas/química , Tensoativos/síntese química , Tensoativos/metabolismo , Tensoativos/toxicidade
16.
Int J Pharm ; 565: 472-480, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31071421

RESUMO

The synergistic effectiveness of chitosan with zinc oxide nanomicelles (CZNPs) on broad spectrum of multidrug resistance (MDR) was previously evidenced in our labs, requiring elucidation of the therapeutic index (TI) for safe in vivo use. This in vitro assessment estimated the effective dose (ED50) of micellar CZNPs for eradication of the MDR Enterococcus faecium 1449 model and the corresponding cytotoxic dose (LD50) against rat small intestinal epithelial cells as functions of TI. In order to visually determine the mechanistic effects of micellar CZNPs on bacterial biofilm size reduction, LIVE/DEAD viability assay was used in conjunction with advanced fluorescence imaging and 3D confocal microscopy. Biofilm quantification was performed through the measure of the fluorescence intensity, using the Biotek Synergy Neo2 for calculating the ED50. To generate the LD50, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay was implemented. Quantification results revealed, at the same concentration (200 µg/mL), micellar CZNPs had average biofilm reduction of approximately 50.22% at 24 h (ED50 = 199.13 µg/mL, LD50 = 240.20 µg/mL, TI = 1.2062), compared to chitosan (15.66%) and ZnO (13.94%) alone. Conclusively, the ED50 of micellar CZNPs on MDR bacterial biofilms (199.13 µg/mL) as a function of TI reveals a promising nanotherapeutic agent in comparison to either Chitosan or ZnO alone.


Assuntos
Quitosana/administração & dosagem , Enterococcus faecalis/efeitos dos fármacos , Micelas , Nanopartículas/administração & dosagem , Óxido de Zinco/administração & dosagem , Animais , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/toxicidade , Farmacorresistência Bacteriana , Enterococcus faecalis/fisiologia , Células Epiteliais/efeitos dos fármacos , Intestino Delgado/citologia , Nanopartículas/toxicidade , Ratos , Óxido de Zinco/toxicidade
17.
Int J Biol Macromol ; 133: 875-880, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31029627

RESUMO

Systems for delivering damaged tissue by immobilization of a bioactive substance or a protein drug for rapid recovery of a patient are being studied. To immobilize drugs using natural polymer, photo-immobilization method has been designed. Immobilization through photo-reaction is a new technology that stabilizes drugs or growth factors for sustained release. Introduction of photo-reactive functional groups into biocompatible natural polymers produces materials applicable to the medical field. Since chitosan is a natural polymer with stability and biocompatibility, this study attempts to use chitosan as a mediator of drug delivery. In addition, If the form of the immobilized biomaterial is made into a micro-sized particle, it can be utilized as an injectable material in addition to the stability of the photo-immobilization. In photo-immobilization in particle form, the probability of exposure to the enzyme in the body is lower than if it is injected into the body in the conventional free state. In addition, since it can be freely injected into a desired target site, it can be used for various medical applications. Therefore, it is expected that various effects of growth factors and drugs can be utilized and additional effects can be obtained by photo-immobilization together with various effects.


Assuntos
Azidas/química , Quitosana/química , Portadores de Fármacos/química , Microesferas , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Quitosana/toxicidade , Portadores de Fármacos/toxicidade , Proteínas Imobilizadas/química , Camundongos , Peso Molecular , Células NIH 3T3 , Soroalbumina Bovina/química
18.
Int J Biol Macromol ; 133: 372-381, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30986460

RESUMO

Advanced local delivery systems are needed as adjunctive treatments for severe injuries with high infection rates, such as open fractures. Chitosan systems have been investigated as antimicrobial local delivery systems for orthopaedic infection but possess mismatches between elution and degradation properties. Derivatives of chitosan were chosen that have enhanced swelling ratios or tailorable degradation properties. A combination of trimethyl chitosan and poly(ethylene glycol) diacrylate chitosan was developed as an injectable local delivery system. Research objectives were elution of antimicrobials for 7 days, degradation as open fractures heal, and cytocompatibility. The derivative combination eluted increased active concentrations of vancomycin and amikacin compared to the non-derivatized chitosan paste, 6 vs. 5 days and 5 vs. 4 days, respectively. The derivative combination degraded slower than non-derivatized paste in an enzymatic degradation study, 14 vs. 3 days, which increased antimicrobial delivery duration. Cytocompatibility of the combination with fibroblast and pre-osteoblast cells exceeds the cell viability standard set in ISO 10993-5. Combination paste requires an increased ejection force of 9.40 N (vs. 0.64 N), but this force was within an acceptable injection force threshold, 80 N. These preliminary results indicate combination paste should be further developed into a clinically useful adjunctive local delivery system for infection prevention.


Assuntos
Antibacterianos/química , Quitosana/química , Quitosana/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Polietilenoglicóis/química , Amicacina/química , Amicacina/farmacologia , Animais , Antibacterianos/farmacologia , Quitosana/toxicidade , Portadores de Fármacos/toxicidade , Injeções , Teste de Materiais , Camundongos , Muramidase/metabolismo , Células NIH 3T3 , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/química , Vancomicina/farmacologia , Viscosidade
19.
Int J Biol Macromol ; 133: 1019-1028, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30986462

RESUMO

Current medical healthcare has no sufficient innovative drug delivery formulations for treating patients with alveolar osteitis. This study presents a portion of research conducted to design, fabricate, and characterize systems for the treatment of alveolar osteitis. The results demonstrate that intra-alveolar formulations can be designed to function as drug carriers, facilitate wound dressing, and promote tissue regeneration. Our aim was to design cone-shaped implants made of microcrystalline chitosan filled with sodium meloxicam, i.e., a nonsteroidal anti-inflammatory agent. SEM analysis revealed the porous structure and monophasic characteristic of the formulation. Moreover, textural analysis demonstrated the effect of different factors (shape, hydration, addition of an active substance) on the hardness, springiness and cohesiveness of the studied systems. The active substance was released in a two-phase process. In vitro biocompatibility tests performed according to ISO 10993-5 confirmed the lack of cytotoxicity of the tested formulations. The designed formulations did not stimulate human THP1-XBlue™ monocytes to activate the transcription nuclear factor NF-κB, which ensures that the performed systems do not induce local inflammation. These initial results indicate that the innovative sodium meloxicam release system can improve safety and efficacy in clinical settings.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Meloxicam/química , Meloxicam/farmacologia , Complicações Pós-Operatórias/tratamento farmacológico , Extração Dentária/efeitos adversos , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/toxicidade , Portadores de Fármacos/toxicidade , Cinética , Meloxicam/uso terapêutico , Camundongos
20.
Int J Biol Macromol ; 132: 374-384, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30914372

RESUMO

Smart hydrogels endowed with self-healing performance, enhanced stability and unique environmental responsiveness were prepared by interpenetrating the crosslinked poly(2-dimethylaminoethyl methacrylate) between the chains of the water-soluble maleoyl-chitosan. The influence of the ratio between the modified polysaccharide and the homopolymer upon the morphological structure and water uptake behaviour of the hydrogels was put in evidence by Scanning electron microscopy and swelling measurements in simulated body fluids. In addition, the synthesised compounds exhibited responsive properties, self-healing behaviour, and great availability like drug delivery systems. The in vitro study evidenced the dependence of the released procaine on the MAC content in the hydrogels, the release mechanism being controlled mainly by Fickian diffusion. The cytotoxicity assay on fibroblast demonstrated improved viability of cells by increasing the modified polysaccharide ratio into hydrogels. The self-repair capacity along with dual pH/thermo-responsiveness and biocompatibility of the hydrogels demonstrate their viability for various bio-applications.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Polímeros/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/toxicidade , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Etilaminas/química , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Hidrogéis/química , Cinética , Teste de Materiais , Fenômenos Mecânicos , Metacrilatos/química , Procaína/química , Reologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA