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1.
J. oral res. (Impresa) ; 11(4): 1-12, jul. 21, 2022. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1427279

RESUMO

Aim: To investigate the precipitate formed from the interaction between 2% lidocaine hydrochloride with adrenaline (LA) with 2.5% sodium hypochlorite (NaOCl) and 0.2% chitosan nanoparticles on root canal dentin, using scanning electron microscopy (SEM). Material and Methods: Sixty mandibular premolars were decoronated, and the root length standardised. The specimens were randomly distributed into the following groups: Group 1 (control): 2% LA mixed with sterile water without root canal instrumentation, Group 2: 2% LA with 2.5% NaOCl in water without root canal instrumentation, and Group 3: 2% LA with 0.2% chitosan nanoparticles in water without root canal instrumentation. Teeth specimens were split and subjected to SEM analysis at cervical, middle, and apical root thirds. On observing precipitate formation in Group 2, 10 premolars were decoronated and treated with 2% LA and 2.5% NaOCl and subjected to root canal instrumentation. Results: Group 1 and Group 3 showed patent dentinal tubules and no precipitate formation. Group 2 showed precipitate blocking dentinal tubules in all the three sections, and the precipitate could not be removed completely after cleaning and shaping. Conclusion: NaOCl forms an insoluble precipitate on interaction with local anaesthetic solution that cannot be removed after chemo-mechanical preparation. Chitosan nanoparticles do not form any such precipitate and show patent dentinal tubules. Hence, chitosan can be used as a flushing irrigant.


Objetivo: Investigar el precipitado formado a partir de la interacción entre el clorhidrato de lidocaína al 2% con adrenalina (LA), el hipoclorito de sodio al 2,5% (NaOCl) y nanopartículas de quitosano al 0,2% en la dentina del conducto radicular, mediante microscopía electrónica de barrido (SEM). Material y Métodos: Se decoraron 60 premolares mandibulares y se estandarizó la longitud de la raíz. Los especímenes se distribuyeron aleatoriamente en los siguientes grupos: Grupo 1 (control): 2% la que fue mezclado con agua estéril sin instrumentación del conducto radicular, Grupo 2: 2% LA con 2,5% de NaOCl sin instrumentación del conducto radicular y Grupo 3: 2 % LA con 0,2% de nanopartículas de quitosano sin instrumentación del conducto radicular. Las muestras de dientes se dividieron y se sometieron a análisis SEM en los tercios radiculares cervical, medio y apical. Al observar la formación de precipitado en el Grupo 2, 10 premolares fueron decorados y tratados con LA al 2% y NaOCl al 2,5% y sometidos a instrumentación de conductos radiculares. Resultado: El Grupo 1 y el Grupo 3 mostraron túbulos dentinarios permeables y sin formación de precipitados. El grupo 2 mostró precipitado que bloqueaba los túbulos dentinarios en las tres secciones, y el precipitado no se pudo eliminar por completo después de limpieza y conformación. Conclusión: el NaOCl forma un precipitado insoluble al interactuar con la solución anestésica local que no se puede eliminar después de la preparación quimiomecánica. Las nanopartículas de quitosano no forman ningún precipitado de este tipo y muestran túbulos dentinarios permeables. Por lo tanto, el quitosano se puede utilizar como irrigante para el lavado.


Assuntos
Humanos , Irrigantes do Canal Radicular/síntese química , Hipoclorito de Sódio/síntese química , Quitosana/síntese química , Lidocaína/síntese química , Dente Pré-Molar , Técnicas In Vitro , Camada de Esfregaço
2.
Carbohydr Polym ; 278: 118941, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973759

RESUMO

Self-assembled microparticles from chitosan (SAMC) was prepared by depolymerization induced by potassium persulfate. Particle size distribution data showed averaged around 5 µm size and SEM indicated the sequential formation of "RBC" shaped particles. Soluble SAMC consists of 'deacetylated' residues as revealed by 13C NMR. SAMC showed antitumor efficacy in human breast cancer cell lines through mitigation in cell proliferation, colony formation and cell migration. Anti-tumor and anti-angiogenic properties of SAMC was found in vivo Ehrlich ascites tumor (EAT) bearing mice model resulting in tumor growth inhibition (EAT control, 17.4 ml; SAMC treated, 6.8 ml) and improved survival potency (15 days). Moreover, the decrease in ascites VEGF secretion (EAT control, 1354 ng; SAMC treated, 351 ng) accompanied with reduction in neovessel formation. Apoptosis induction by SAMC was confirmed by DNA fragmentation, caspase activities and fluorescence staining methods respectively. SAMC may be a safe candidate for anti-tumor dietary supplement production in food industry.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Ehrlich/tratamento farmacológico , Quitosana/farmacologia , Neovascularização Patológica/tratamento farmacológico , Animais , Configuração de Carboidratos , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quitosana/síntese química , Quitosana/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neovascularização Patológica/patologia
3.
Carbohydr Polym ; 278: 118969, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973784

RESUMO

We prepared a new injectable thermogel to enhance the efficiency of inner ear delivery of dexamethasone (DEX). Hexanoyl glycol chitosan (HGC) was synthesized and evaluated as an amphiphilic thermogel (Tgel ~ 32 °C) for use as a solubilizing agent as well as an injectable carrier for intratympanic delivery of the hydrophilic and hydrophobic forms of DEX. Various thermogel formulations with different drug types and concentrations were prepared, and their physicochemical and thermogelling properties were characterized by 1H NMR, ATR-FTIR, and rheometer. They exhibited versatile release kinetics from several hours to more than 2 weeks, depending on drug type and concentration. Our formulations further showed good residual stability for more than 21 days without any cytotoxicity or inflammation in the middle and inner ear and could deliver a considerably high drug concentration into the inner ear. Therefore, HGC thermogel has great potential as an effective and safe formulation for inner ear drug delivery.


Assuntos
Quitosana/química , Dexametasona/farmacologia , Sistemas de Liberação de Medicamentos , Orelha Interna/efeitos dos fármacos , Temperatura , Animais , Quitosana/administração & dosagem , Quitosana/síntese química , Dexametasona/administração & dosagem , Dexametasona/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Composição de Medicamentos , Géis/administração & dosagem , Géis/síntese química , Géis/química , Cobaias , Masculino , Estrutura Molecular
4.
Carbohydr Polym ; 278: 118984, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973791

RESUMO

The traditional solvent casting method for preparing chitosan-based materials has limited productivity relative to the productivity of thermomechanical processing. Consequently, the thermomechanical processing technique was evaluated as a way to increase chitosan production. The role of citric acid (CA) as a destructuring and crosslinking agent during such processing was examined. SEM images revealed robust fibers that were associated with a superior mechanical strength (145%), which were produced after thermomechanical processing of chitosan in the presence of CA. Based on articles reviewed, this is the first time that this structure has been closely observed in the microstructure of chitosan-based materials. FTIR and XRD characterization showed the occurrence of chemical crosslinking and the successful destructuring of chitosan powder by CA during processing. Compared to acetic acid, the use of CA led to the development of materials with a homogeneous morphology and good physicochemical and mechanical properties that are suitable for biomedical applications.


Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Ácido Cítrico/química , Temperatura , Materiais Biocompatíveis/síntese química , Configuração de Carboidratos , Quitosana/síntese química , Estresse Mecânico
5.
Carbohydr Polym ; 278: 119000, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973802

RESUMO

Designing adhesive hydrogel wound dressings with inherent antibacterial and antioxidant properties is desirable to treat cutaneous full-thickness injuries in clinical care. Herein, a series of photo-induced Schiff base crosslinking-based adhesive hydrogels with promising traits are designed and prepared through Diels-Alder (DA) reactions between functional groups-grafted carboxymethyl chitosan (CMCS) and a photo-responsive polyethylene glycol (PEG) crosslinker. The quaternary ammonium and phenol groups in modified CMCS endows hydrogels excellent antibacterial and antioxidant properties. Upon UV (365 nm) irradiation, the generated o-nitrosobenzaldehyde from the photo-isomerization of o-nitrobenzyl in PEG derivative can subsequently crosslink with amino groups on tissue interfaces via Schiff base, endowing the hydrogel with well adhesiveness. Additionally, the hydrogel exhibits good BSA adsorption capacity, cytocompatibility and hemostatic property. The in vivo full-thickness skin defect study on mice indicates that the multi-functional hydrogel with considerable collagen deposition and vascularization capacities can be an effective and promising adhesive dressing for improving wound healing.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Quitosana/análogos & derivados , Hidrogéis/farmacologia , Adesivos Teciduais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Galinhas , Quitosana/síntese química , Quitosana/química , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Feminino , Hidrogéis/síntese química , Hidrogéis/química , Camundongos , Camundongos Endogâmicos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Tamanho da Partícula , Processos Fotoquímicos , Picratos/antagonistas & inibidores , Pele/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Suínos , Adesivos Teciduais/síntese química , Adesivos Teciduais/química , Raios Ultravioleta
6.
Int J Biol Macromol ; 195: 75-85, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34883163

RESUMO

The aim of this study was to develop a green method to fabricate a novel CS modified N-(4-hydroxyphenyl)- methacrylamide conjugate (CSNHMA) and to evaluate its biomedical potential. CSNHMA has been prepared by a simple method via aza Michael addition reaction between CS and N- (4-hydroxyphenyl)-methacrylamide (NHMA) in ethanol. Its structural and morphological properties were characterized by various analysis techniques. The obtained results confirmed that a highly porous network structure of CSNHMA was successfully synthesized via aza Michael addition reaction. Consequently, it was analyzed as a drug and gene carrier. CSNHMA/pGL3 showed an enhanced buffering capacity due to the presence of NHMA moiety leading to higher transfection efficiency in all cancer cells (A549, HeLa and HepG2) as compared to native CS and Lipofectamine®. Therefore, these findings clearly support the possibility of using CSNHMA as a good transfection agent. For in vitro drug release study, we prepared CSNHMA nanoparticles (NPs) and curcumin loaded CSNHMA NPs of size <230 nm respectively via the non-toxic ionic gelation route and the encapsulation efficiency of drug was found to be 77.03%. In vitro drug release studies demonstrated a faster and sustained release of curcumin loaded CSNHMA NPs at pH 5.0 compared to physiological pH.


Assuntos
Acrilamidas/química , Quitosana/síntese química , Curcumina/farmacologia , Luciferases/genética , Células A549 , Sequência de Carboidratos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Curcumina/química , Preparações de Ação Retardada , Portadores de Fármacos , Química Verde , Células HeLa , Células Hep G2 , Humanos , Tamanho da Partícula , Fosfatidiletanolaminas/farmacologia , Porosidade , Transfecção
7.
Carbohydr Polym ; 277: 118755, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34893210

RESUMO

Recent advancements in gene delivery systems that specifically target a variety of cancer types have increased demand for tissue-specific gene therapy. The current study describes the synthesis of a copolymer (GPgWSC) composed of a polyethylenimine (PEI)-grafted water-soluble chitosan (WSC) and gambogic acid (GA). It was validated as a ligand capable of enabling targeted attachment to transferrin receptors in HCT116 cancer cell lines. GPgWSC demonstrated superior antitumor activity in vitro in HCT116 compared to LoVo or MCF-7 cell lines, facilitated by the apoptotic activity of psiRNA-hBCL2. Pre-incubation of transferrin significantly inhibited GFP expression in the GPgWSC polyplex, demonstrating that GA is an extremely effective transferrin receptor targeting molecule. Additionally, in the HCT116-bearing mouse model, the tumor mass of PBS-treated mice increased to 2270 mm2 after 22 days, but the injection of GPgWSC polyplex significantly reduced the mass-increasing rate as a mass size of 248 mm2.


Assuntos
Antineoplásicos/farmacologia , Quitosana/análogos & derivados , Polietilenoimina/análogos & derivados , Polímeros/farmacologia , Receptores da Transferrina/antagonistas & inibidores , Xantonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quitosana/síntese química , Quitosana/química , Quitosana/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Polietilenoimina/síntese química , Polietilenoimina/química , Polietilenoimina/farmacologia , Polímeros/química , Receptores da Transferrina/genética , Xantonas/química
8.
Carbohydr Polym ; 277: 118870, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34893275

RESUMO

The aim of this study is both to design the chitosan (Chi) nanoparticles with different Mw containing the phosphoester bonds and increase their amino function for the transfection. The phosphorylamine-modification of Chi and depolymerized Chi (DChi) was realized using o-phosphorylethanolamine (o-PEA) and characterized, for the first time. The nanoparticles (nMChi and nMDChi) were prepared by ionic gelation and their particle size, polydispersity index (PDI), zeta potential, stability, gene binding capacity and cytotoxicity were examined. The effects of the Mw of Chi on the cytotoxicity, gene binding capacity, and in vitro transfection efficiency of the nanoparticles on Human Embryonic Kidney 293 (HEK293) cells were also examined. Green Fluorescent Protein Circular Plasmid DNA (pEGFN1) loaded nanoparticles (gnMChi and gnMDChi) were used in the transfection. This study showed that the Mw of phosphorylamine-modified Chi significantly affected the characteristics, cytotoxicity, gene binding capacity and transfection efficiency of the nanoparticles.


Assuntos
Aminas/química , Quitosana/química , Configuração de Carboidratos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/síntese química , Quitosana/farmacologia , Células HEK293 , Humanos , Peso Molecular , Nanopartículas/química , Tamanho da Partícula
9.
Carbohydr Polym ; 277: 118871, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34893276

RESUMO

In order to develop better wound dressings, a novel chitosan hydrogel (Cn-Nm gel) was designed and fabricated by using aldehyde-4-arm polyethylene glycol (4r-PEG-CHO) to crosslink the chitosan dissolved in alkaline solution, amino-4-arm polyethylene glycol (4r-PEG-NH2) was chosen as the additive simultaneously. The special dissolution technique and macromolecular crosslinking structure endows the Cn-Nm gels with better performance than that of gels prepared by acid dissolving method with micromolecule crosslinker. First, Cn-Nm gels own strong toughness with 500 kPa tensile strength and 1000% elongation, about 400% swelling ratio and fast water absorption rate. Second, about 300 kPa adhesive strength and strippability between the gels and skin is achieved. More importantly, Cn-Nm gels show nearly 100% antibacterial rate towards Escherichia coli and Staphylococcus aureus. Excellent biocompatibility is also proved by the mouse fibroblasts tests. All of the performance makes this developed chitosan-based gel be the potential candidate as a wound dressing.


Assuntos
Antibacterianos/farmacologia , Bandagens , Materiais Biocompatíveis/farmacologia , Reagentes de Ligações Cruzadas/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Quitosana/síntese química , Quitosana/química , Quitosana/farmacologia , Reagentes de Ligações Cruzadas/síntese química , Reagentes de Ligações Cruzadas/química , Escherichia coli/efeitos dos fármacos , Hidrogéis/síntese química , Hidrogéis/química , Hidrogéis/farmacologia , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Staphylococcus aureus/efeitos dos fármacos
10.
Carbohydr Polym ; 277: 118882, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34893285

RESUMO

Hydrophobized chitosan derivatives, hexyl chitosan (HCS), dodecyl chitosan (DCS), and phthaloyl chitosan (PhCS) of approximately 30 and 50% degree of substitution (%DS) reacted with glycidyltrimethylammonium chloride (GTMAC) to incorporate hydrophilic positively charged groups of N-[(2-hydroxyl-3-trimethylammonium)propyl] and yielded amphiphilic quaternized chitosan derivatives. They can assemble into spherical nanoparticles with a hydrodynamic diameter of ~100-300 nm and positive ζ-potential values (+15 to +56). Their anti-biofilm efficacy was evaluated against the dental caries pathogen, Streptococcus mutans. Among all derivatives, the one having 30%DS of hexyl group and prepared by reacting with 1 mol equivalent of GTMAC (H30CS-GTMAC) showed the best performance in terms of its aqueous solubility, the lowest minimum inhibitory concentration (138 µg/mL) and the minimum bactericidal concentration (275 µg/mL) which are superior to the unmodified chitosan. Its equivalent anti-biofilm efficacy to that of chlorhexidine suggests that it can be a greener antibacterial agent for oral care formulations.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Quitosana/farmacologia , Streptococcus mutans/efeitos dos fármacos , Tensoativos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Configuração de Carboidratos , Quitosana/síntese química , Quitosana/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Tensoativos/síntese química , Tensoativos/química
11.
Carbohydr Polym ; 275: 118702, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742428

RESUMO

The high molecular weight of chitin, as a biopolymer, challenges its extraction due to its insolubility in the solvents. Also, chitosan, as the N-deacetylated form of chitin, can be employed as a primary material for different industries. The low mechanical stability and poor plasticity of chitosan films, as a result of incompatible interaction between chitosan and the used solvent, have limited its industrialization. Deep eutectic solvents (DESs), as novel solvents, can solve the extraction difficulties of chitin, and the low mechanical stability and weak plasticity of chitosan films. Also, DESs can be considered for the different chitosan and chitin productions, including chitin nanocrystal and nanofiber, N,N,N-trimethyl-chitosan, chitosan-based imprinted structures, and DES-chitosan-based beads and monoliths. This review aims to focus on the preparation and characterization (chemistry and morphology) of DES-chitin-based and DES-chitosan-based structures to understand the influence of the incorporation of DESs into the chitin and chitosan structure.


Assuntos
Quitina/química , Quitosana/química , Solventes Eutéticos Profundos/química , Quitina/síntese química , Quitosana/síntese química , Estrutura Molecular
12.
Int J Biol Macromol ; 195: 49-58, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34856218

RESUMO

This study aimed to develop a plasticized starch (PS) based film loaded with chitosan nanoparticles (CNPs, 1, 2, 3, and 4%) as a reinforcing and antibacterial agent. We examined the morphology, biodegradability, mechanical, thermo-mechanical, and barrier properties of the PS/CNPs films. The antimicrobial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria was investigated by colony forming unit (CFU) and disc diffusion methods. A dense structure was obtained for all PS/CNPs films and, thus, their complete biodegradation occurred in more days than neat PS. The increase in the CNPs percentage led to improved mechanical behaviour and barrier properties. PS-CNPs composite films revealed inhibition zones against both E. coli and S. aureus, with the 100% reduction in CFU against S. aureus. The current study exhibited that PS-CNPs films were more effective in inhibiting bacteria growth than neat PS film, confirming the composite films potential application as antimicrobial food packaging.


Assuntos
Anti-Infecciosos/farmacologia , Plásticos Biodegradáveis/farmacologia , Quitosana/farmacologia , Amido/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Quitosana/síntese química , Quitosana/química , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Embalagem de Alimentos , Nanocompostos , Tamanho da Partícula , Permeabilidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
13.
Braz. J. Pharm. Sci. (Online) ; 58: e191120, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1394048

RESUMO

Abstract The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role.


Assuntos
Cicatrização , Hidrogéis/análise , Quitosana/síntese química , Fator de Crescimento Epidérmico , Álcool de Polivinil/farmacologia , Ferimentos e Lesões/classificação , Técnicas In Vitro/métodos , Técnicas de Cultura de Células/métodos , Proliferação de Células/genética , Absorção
14.
ACS Appl Mater Interfaces ; 13(45): 53541-53552, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34726373

RESUMO

Torealize intelligent and personalized medicine, it is a huge challenge to develop a hydrogel dressing that can be used as a sensor to monitor human health in real-time while promoting wound healing. Herein, an injectable, self-healing, and conductive chitosan-based (CPT) hydrogel with pH responsiveness and intrinsic antibacterial properties was fabricated via a Schiff base linkage and a hydrogen bond. Due to the introduction of Schiff base bonds, the injectable CPT hydrogel exhibits various excellent properties, such as pH responsiveness to sol-gel transition, self-healing properties, and broad-spectrum antibacterial properties even without additional antibacterial agents. In vitro experiments verify the excellent biocompatibility of the as-prepared hydrogel. An in vivo experiment in a mouse full-thickness skin-wound model was performed to confirm the outstanding effect on wound healing. Meanwhile, as epidermal sensors, the conductive hydrogel that perceives various human activities in real-time could provide the real-time analysis of the patient's healthcare information. Based on these excellent properties, the CPT hydrogel, as a biological dressing with a sensing function, lays a solid foundation for the further realization of personalized medicine.


Assuntos
Antibacterianos/farmacologia , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Hidrogéis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/síntese química , Quitosana/química , Condutividade Elétrica , Epiderme , Humanos , Hidrogéis/síntese química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula
15.
J Mater Chem B ; 9(41): 8694-8707, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34622266

RESUMO

Dental plaque biofilms are believed to be one of the principal virulence factors in periodontitis resulting in tooth loss. Traditional mouthwashes are limited due to the continuous flow of saliva and poor drug penetration ability in the biofilm. Herein, we fabricated an antibiotic delivery platform based on natural polysaccharides (chitosan and cyclodextrin) as a novel mouthwash for the topical cavity delivery of minocycline. The penetration and residence mechanisms demonstrate that the platform can prolong the residence time up to 12 h on biofilms. Furthermore, sustained release can enhance the penetration of drugs into biofilms. In vitro antibiofilm experimental results indicated that the mouthwash effectively kills bacteria and eradicate biofilms. Effective treatment in vivo was confirmed by the significantly reduced dental plaque and alleviated inflammation observed in a rat periodontitis model. In summary, this novel platform can improve antibiofilm efficiency and prevent drugs from being washed away by saliva, which may provide benefits for many oral infectious diseases.


Assuntos
Antibacterianos/farmacologia , Quitosana/farmacologia , Ciclodextrinas/farmacologia , Antissépticos Bucais/farmacologia , Periodontite/tratamento farmacológico , Porphyromonas gingivalis/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Quitosana/síntese química , Quitosana/química , Ciclodextrinas/síntese química , Ciclodextrinas/química , Placa Dentária/tratamento farmacológico , Placa Dentária/microbiologia , Placa Dentária/patologia , Masculino , Testes de Sensibilidade Microbiana , Antissépticos Bucais/síntese química , Antissépticos Bucais/química , Periodontite/microbiologia , Periodontite/patologia , Ratos , Ratos Sprague-Dawley
16.
Phys Chem Chem Phys ; 23(39): 22601-22612, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34591050

RESUMO

Chitosan can associate in the presence of polyphosphates into insoluble hydrogels capable of drug encapsulation and safe and efficient release. On the one hand, chitosan hydrogels were synthesized using the phytate anion as a crosslinking agent and were characterized by employing dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). On the other hand, an effective chitosan-phytate model with atomistic details was created to examine the underlying physical crosslinking pattern, and the structure and dynamics of the chitosan-phytate complex were systematically investigated by using molecular dynamics (MD) simulations. To harbor the crosslinker potential for obtaining chitosan-based hydrogels, the impact of the phytate concentration and the functional groups of the chitosan on the reticulation process was addressed. The phytate association was determined by the phosphates' capacity for H-bonding to the amine and hydroxyl groups belonging to two consecutive glucosidic units. The physical crosslinking pattern was determined by the number of chitosan chains bound by one phytate anion and the phytate orientation relative to the glucopyranose neighbors. Cross-linking of two up to six chitosan chains mediated by a phytate anion represented favorable states, and the number distribution of cross-linked chains depended on the phytate concentration. The circular distribution of the cross-linkable phosphates regulated the nearly isotropic orientation of the chitosan chains and phytate at the junction, and the variety of topological crosslinking demonstrated the phytate ion's potential for developing chitosan-based hydrogels with improved structural attributes.


Assuntos
Quitosana/química , Simulação de Dinâmica Molecular , Quitosana/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576093

RESUMO

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.


Assuntos
Carbono/química , Sistemas de Liberação de Medicamentos , Olho/efeitos dos fármacos , Olho/diagnóstico por imagem , Géis/farmacologia , Temperatura , Animais , Humor Aquoso/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Quitosana/análogos & derivados , Quitosana/síntese química , Quitosana/química , Diclofenaco/farmacologia , Liberação Controlada de Fármacos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Irritantes/toxicidade , Nanopartículas/ultraestrutura , Soluções Oftálmicas/farmacologia , Espectroscopia Fotoeletrônica , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Int J Biol Macromol ; 190: 351-359, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492248

RESUMO

In this study, a pH-responsive drug carrier was developed for the controllable release of drugs in the gastric environment. Chitosan (CS), a pH-sensitive biopolymer, and laponite RD (LAP), a nano-clay with a high drug-loading capability, were used to design the new carrier. Hydroxyapatite (HA) was grafted into CS/LAP matrix through a simple co-precipitation technique to overcome the burst release of the CS/LAP. The structural analysis and swelling tests of products demonstrated that the co-precipitation method has led to the penetration of HA nanoparticles inside the CS/LAP matrix and occupying its hollow pores. Occupation of the empty pores can lead to the entrapment of drug molecules, thereby reducing the release rate. The nanocomposite showed a high loading capacity to ofloxacin as a drug model. The effects of HA content on release behavior of nanocomposite were investigated at simulated gastric (pH 1.2) and intestine (pH 7.4) environments. The results indicated a high pH sensitivity for CS/LAP/HA. HA grafting reduced the release rate remarkably regardless of pH. The release rate of CS/LAP/HA decreased by 44-63% in pH 1.2 and 41-51% in pH 7.4 compared to CS/LAP. Kinetic studies indicated that grafting the HA in CS/LAP has changed the drug release mechanism.


Assuntos
Quitosana/química , Durapatita/química , Hidrogéis/química , Silicatos/química , Antibacterianos/farmacologia , Quitosana/síntese química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Durapatita/síntese química , Escherichia coli/efeitos dos fármacos , Hidrogéis/síntese química , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Ofloxacino/farmacologia , Silicatos/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Termogravimetria , Difração de Raios X
19.
Carbohydr Polym ; 273: 118592, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560993

RESUMO

N-trimethyl chitosan (TMC) is a multifunctional polymer that can be used in various nanoparticle forms in the pharmaceutical, nutraceutical and biomedical fields. In this study, TMC was used as a mucoadhesive adjuvant to enhance the oral bioavailability and hence antitumour effects of gemcitabine formulated into nanocomplexes composed of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) conjugated with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). A central composite design was applied to achieve the optimal formulation. Cellular uptake and drug transportation studies revealed the nanocomplexes permeate over the intestinal cells via adsorptive-mediated and caveolae-mediated endocytosis. Pharmacokinetic studies demonstrated the oral drug bioavailability of the nanocomplexes was increased 5.1-fold compared with drug solution. In pharmacodynamic studies, the formulation reduced tumour size 3.1-fold compared with the drug solution. The data demonstrates that TMC modified nanocomplexes can enhance gemcitabine oral bioavailability and promote the anticancer efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Quitosana/síntese química , Quitosana/química , Quitosana/metabolismo , Desoxicitidina/química , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/síntese química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Ratos Sprague-Dawley , Vitamina E/síntese química , Vitamina E/química , Vitamina E/metabolismo , Gencitabina
20.
Carbohydr Polym ; 273: 118601, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561001

RESUMO

A new type of biocompatible buffers based on zwitterionic polyaminosaccharides is reported. The carboxy- and amino-groups containing carboxymethyl chitosan (CM-CS) was synthesized and reacted with hydrochloric/acetic acid resulting in CM-CS-HCl and CM-CS-HAc buffers with buffering capacity of 20.6 and 15.2 mM/pH. The new buffers were comprehensively characterized for their physicochemical properties and checked on enzymatic reactions of acetylcholinesterase (AChE) and alkaline phosphatase (ALP). Their performance was compared to the phosphate and Tris buffers. The chloride-free, CM-CS-HAc demonstrated excellent buffering activity with Michaelis constants of 0.50 and 1.00 mM and maximum reaction rates of 5.62 and 2.26 µmol/min/mL for AChE and ALP reactions, respectively. Toxicity studies on stress-sensitive bioreporter bacteria verified nontoxicity of CM-CS-HAc. Zwitterionic polyaminosaccharides overcome drawbacks of monomeric buffers, such as interference with enzyme active sites, cell membrane injury and purification difficulties. Therefore, they may become the next generation of effective buffers for biological and biochemical applications.


Assuntos
Quitosana/análogos & derivados , Acetilcolinesterase/química , Acetiltiocolina/química , Fosfatase Alcalina/química , Soluções Tampão , Quitosana/síntese química , Quitosana/toxicidade , Escherichia coli/efeitos dos fármacos , Ponto Isoelétrico , Nitrofenóis/química , Compostos Organofosforados/química , Solubilidade , Água/química
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