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1.
Org Biomol Chem ; 17(42): 9321-9335, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31612902

RESUMO

Alginate, an anionic polysaccharide, is an important industrial biomaterial naturally harvested from seaweed. Many of its important physicochemical properties derive from the presence of charged carboxylate groups presented as uronic acids within the polysaccharide backbone. An ability to modify these carboxylates with alternate functional groups would enable the design and implementation of new alginate systems possessing different physicochemical properties. We present herein our approach to the chemical synthesis of alginate disaccharides, modified at the carboxylate C6 position with bioisosteric hydroxamate residues. The synthesis and utilisation of C6-hydroxamate donor and acceptor building blocks enables a first access to protected α- and ß-linked hydroxamate-containing disaccharides, additionally equipped with a functional tether at the reducing terminus. The evaluation of these building blocks for chemical glycosylation demonstrates the incorporation of bioisosteric functional groups into an alginate disaccharide backbone and highlights the important contribution of both acceptor and donor reactivity underpinning uronate glycosylations.


Assuntos
Alginatos/química , Alginatos/síntese química , Ácidos Hidroxâmicos/química , Configuração de Carboidratos , Glicosilação
2.
Int J Nanomedicine ; 14: 7743-7758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571874

RESUMO

Purpose: Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized. Materials and methods: A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles. Results: They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy. Conclusion: CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.


Assuntos
Alginatos/química , Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Vitamina B 12/química , Administração Oral , Alginatos/síntese química , Animais , Células CACO-2 , Morte Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina B 12/síntese química
3.
Carbohydr Polym ; 223: 115070, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31427031

RESUMO

A biodegradable, near-infrared (NIR) - responsive hydrogel is one of the most promising strategies as a remotely triggered drug carrier. In this study, novel NIR-responsive hydrogels based on alginate structures were prepared for controllable drug release. The hydrogels were formed rapidly by reacting norbornene-functionalized alginates and tetrazine cross-linkers containing diselenide bonds via inverse electron demand Diels-Alder click chemistry. In order to manipulate their properties, we prepared hydrogels with various cross-linking densities. NIR sensitive indocyanine green (ICG) and a drug, doxorubicin (DOX) were incorporated in the hydrogel matrix during gelation. The hydrogels showed a suppressed release profile under physiological conditions, while NIR light triggered a rapid release of DOX. Under NIR-light irradiation, ICG generated reactive oxygen species which could decompose diselenide bonds in the hydrogel matrix, inducing the gel-sol transition and release of entrapped DOX. The degradation of hydrogels could be also controlled by the ratio of the precursors.


Assuntos
Alginatos/química , Portadores de Fármacos/química , Hidrogéis/química , Compostos Organosselênicos/química , Alginatos/síntese química , Alginatos/efeitos da radiação , Doxorrubicina/química , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Compostos Heterocíclicos com 1 Anel/síntese química , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/efeitos da radiação , Hidrogéis/síntese química , Hidrogéis/efeitos da radiação , Peróxido de Hidrogênio/química , Raios Infravermelhos , Norbornanos/síntese química , Norbornanos/química , Norbornanos/efeitos da radiação , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/efeitos da radiação
4.
Carbohydr Polym ; 221: 221-230, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31227162

RESUMO

A highly efficient flame-retardant and ultra-low-smoke-toxicity biodegradable material, poly(vinyl alcohol) (PVA)/alginate/montmorillonite (MMT) composite aerogel, was fabricated by a new environment-friendly two-step crosslinking strategy using borate and calcium ions. Compressive and specific moduli of the crosslinked PVA/alginate/MMT (P4A4M4/BA/Ca) aerogel increased to 7.2- and 1.9-folds those of the non-crosslinked aerogel, respectively, and the limited oxygen index value increased to 40.0%. Cone calorimeter tests revealed that the total heat release and peak heat release rate values of the P4A4M4/BA/Ca composite aerogel distinctly decreased. Remarkably, the total smoke release value of the P4A4M4/BA/Ca aerogel was considerably lower than those of non-crosslinked PVA composite aerogels, indicating its superior smoke suppression ability and high fire hazardous safety. The flame-retardancy mechanism of the crosslinked P4A4M4/BA/Ca composite aerogels involved a combination of the gaseous phase and condensed phase flame retardancy. The high-performance PVA/alginate/MMT biodegradable composite aerogels with good sustainability is a promising alternative to conventional flame-retardant foams.


Assuntos
Alginatos/química , Bentonita/química , Retardadores de Chama/síntese química , Hidrogéis/química , Álcool de Polivinil/química , Alginatos/síntese química , Alginatos/toxicidade , Bentonita/síntese química , Bentonita/toxicidade , Boratos/química , Reagentes para Ligações Cruzadas/química , Retardadores de Chama/toxicidade , Hidrogéis/síntese química , Hidrogéis/toxicidade , Álcool de Polivinil/síntese química , Álcool de Polivinil/toxicidade , Fumaça
5.
Colloids Surf B Biointerfaces ; 181: 158-165, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129522

RESUMO

Creating an appropriate antibacterial disinfection system without forming any harmful compounds is still a major challenge and calls for new technologies for efficient disinfection and microbial control. Towards this aim, we report on the elaboration of biodegradable and biocompatible polymeric nanocapsules, also called hollow nanoparticles, for potential applications in antibiotic therapy. These nanomaterials are based on the self-assembly of charged polysaccharides, namely chitosan and alginate, onto gold nanoparticles as a sacrificial matrix (60 nm). Electrostatic interactions between the protonated amine groups of chitosan (+35 mV) and the carboxylate groups of alginate (- 20 mV) are the driving attraction force enabling the elaboration of well-ordered multilayer films onto the spherical substrate. The removal of the colloidal gold, via cyanide-assisted hydrolysis, is evidenced by time-dependent variation of the gold spectroscopic signature (30 min is required). TEM shows the obtention of nanocapsules. An inhibitory effect of these particles has been demonstrated during the growth of two representative bacteria in a liquid medium: Staphylococcus aureus (Gram-positive) (from 4.6% to 16.3% for gold nanomaterials + and from 18.6% to 34.9% for (chi+/alg-)n-chi+ nanocapsules) and Escherichia coli (Gram-negative) (from 5.4% to 20% for gold nanomaterials and from 23.7% to 40% for (chi+/alg-)n-chi+ nanocapsules). Acridine orange staining demonstrated the bactericidal effect of chitosan-based capsules. These findings demonstrate that (chitosan/alginate)n capsules can be exploited as new antibacterial material. Thus, we present a complementary approach to classical nanoparticles prepared by complexation between alginate and chitosan or other materials.


Assuntos
Antibacterianos/farmacologia , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/química , Staphylococcus aureus/efeitos dos fármacos , Alginatos/síntese química , Alginatos/química , Alginatos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Quitosana/síntese química , Quitosana/química , Ouro/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Propriedades de Superfície
6.
Mater Sci Eng C Mater Biol Appl ; 101: 323-329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029325

RESUMO

In this study, the antifungal activity rate of alginate-CuO bionanocomposite was assessed against Aspergillus niger using colony forming units (CFU) and disc diffusion methods. Employing the Taguchi method, nine experiments were designed for the synthesis of alginate-CuO nanocomposite with the highest antifungal activity. The nanocomposite synthesized under the conditions of experiment 5 (4 mg/mL CuO nanoparticles and 1 mg/mL alginate biopolymer with stirring time of 90 min) showed the greatest inhibition rate on fungal growth (83.17%). In the optimum conditions for the synthesis of alginate-CuO nanocomposite with the highest antifungal activity the second level of CuO NPs (14.14%), alginate biopolymer (8.16%) and stirring time (5.63%) showed the best improvement performance on inhibiting the fungal growth. The results of ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM) and X-ray powder diffraction (XRD) confirmed the formation of alginate-CuO nanocomposite. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) indicated that the thermal stability of alginate biopolymer and CuO nanoparticles were improved by the formation of the nanocomposite. Due to the favorable properties of alginate-CuO nanocomposite, its antifungal feature can be used in various biomedical fields.


Assuntos
Alginatos/síntese química , Alginatos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Materiais Biocompatíveis/síntese química , Cobre/farmacologia , Nanocompostos/química , Temperatura Ambiente , Alginatos/química , Antifúngicos/química , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cobre/química , Testes de Sensibilidade Microbiana , Nanocompostos/ultraestrutura , Espectrofotometria Ultravioleta , Termogravimetria , Difração de Raios X
7.
J Colloid Interface Sci ; 539: 497-503, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30611045

RESUMO

Alginate hydrogel particles are promising delivery systems for protein encapsulation and controlled release because of their excellent biocompatibility, biodegradability, and mild gelation process. In this study, a facile microfluidic approach is developed for making uniform core-shell hydrogel microparticles. To address the challenge of protein retention within the alginate gel matrix, poly(ethyleneimine) (PEI)- and chitosan-coated alginate microparticles were fabricated demonstrating improved protein retention as well as controlled release. Furthermore, a model protein ovalbumin was loaded along with delta inulin microparticulate adjuvant into the water-core of the alginate microparticles. Compared to those microparticles with only antigen loaded, the antigen + adjuvant loaded microparticles showed a delayed and sustained release of antigen. This microfluidic approach provides a convenient method for making well-controlled alginate microgel particles with uniform size and controlled properties, and demonstrates the ability to tune the release profiles of proteins by engineering microparticle structure and properties.


Assuntos
Alginatos/síntese química , Preparações de Ação Retardada/química , Técnicas Analíticas Microfluídicas , Microesferas , Ovalbumina/química , Alginatos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Tamanho da Partícula , Propriedades de Superfície
8.
J Pharm Biomed Anal ; 162: 215-224, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30265981

RESUMO

This paper reports on the synthesis of a novel molecularly imprinted composite film using the mathematical modeling. This composite was then used in the electrode modification for the determination of theophylline. The ratio of monomer to template in optimum condition was obtained to be 4. The modification of electrode was performed in the presence of theophylline through the electropolymerization of arginine on the composite of sodium alginate/multiwalled carbon nanotubes (SA-MWCNTs), which had been coated on glassy carbon electrode (GCE). The SA-MWCNTs composite with netlike morphology demonstrated high conductivity and electrocatalytic activity. Cyclic voltammogram of modified electrode (MIP/SA-MWCNTs/GCE) in the presence of theophylline showed a sensitive anodic peak in 1170 mV in buffer solution of phosphate (pH 7.0). The investigation and optimization of the effective factors on the response and electrochemical behavior of target theophylline were accurately done on the surface of the modified electrode. Theophylline response was linearly within the range of 0.01-60.0 µM with detection limit of 3.2 nM. Regarding the added standards, the recoveries were values between 93.4-105%. The function of this electrode was satisfactory in the determination of theophylline in real samples like theophylline tablet, theophylline oral solution and human plasma samples.


Assuntos
Alginatos/síntese química , Projeto Auxiliado por Computador , Química Verde , Microeletrodos , Impressão Molecular , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Nanotubos de Carbono/química , Peptídeos/síntese química , Teofilina/sangue , Condutividade Elétrica , Desenho de Equipamento , Humanos , Limite de Detecção , Soluções Farmacêuticas , Reprodutibilidade dos Testes , Comprimidos
9.
Free Radic Biol Med ; 129: 177-185, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30223019

RESUMO

Previous studies have confirmed that protein tyrosine phosphatase 1B (PTP1B) can promote tumour progression in non-small cell lung cancer (NSCLC). Vanadyl alginate oligosaccharides (VAOS) is a new coordination compounds that possesses a good PTP1B inhibitory activity. However, the potent anticancer efficacy of VAOS in human NSCLC requires further study. In this study, VAOS exhibited effective inhibitory effects in NSCLC both in cultured cells and in a xenograft mouse model. VAOS was further identified to induce NSCLC cell apoptosis through activating protein kinase B (AKT) to elevate intracellular reactive oxygen species (ROS) levels by increasing in oxygen consumption and impairing the ROS-scavenging system. Neither silencing of PTP1B by siRNA nor transient overexpression of PTP1B had an effect on the AKT phosphorylation triggered by VAOS, indicating that PTP1B inhibition was not involved in VAOS-induced apoptosis. Through phosphorus colorimetric assay, we demonstrated that VAOS notably inhibited phosphatase and tensin homologue deleted on chromosome 10 (PTEN) dephosphorylation activity, another member of the protein tyrosine phosphatases (PTPases)-upstream factor of AKT. Interestingly, PTEN knockdown sensitized cells to VAOS, whereas ectopic expression of PTEN markedly rescued VAOS-mediated lethality. In vivo, VAOS treatment markedly reduced PTEN activity and tumour cell burden with low systemic toxicity. Thus, our data not only provided a new therapeutic drug candidate for NSCLC, but presented new understanding into the pharmacological research of VAOS.


Assuntos
Alginatos/farmacologia , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Vanadatos/farmacologia , Células A549 , Alginatos/síntese química , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Vanadatos/síntese química , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Int J Biol Macromol ; 120(Pt A): 775-782, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30170057

RESUMO

Diabetes mellitus is a highly prevalent metabolic and chronic disease affecting millions of people in the world. The most common route of insulin therapy is the subcutaneous injection due to its low bioavailability and enzymatic degradation. The search for effective and high patient compliance insulin delivery systems has been a major challenge over many decades. The polysaccharide-based nanoparticles as delivery vehicles for insulin oral administration have recently attracted substantial interests. The present review highlights the recent advances on the development of nanoparticles prepared from polysaccharides, including chitosan, alginate, dextran and glucan, for oral delivery of insulin, overcoming multiple barriers in gastrointestinal tract. The aims of this review are first to summarize the strategies that have been applied in the past 5 years to fabricate polysaccharide-based nanoparticles for insulin oral delivery, and then to provide in-depth understanding on the mechanisms by which such nanoparticles protect insulin against degradation in the digestive tract and provide sustained release to enhance mucus permeation and transepithelial transport of insulin administered via oral route.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Insulina/uso terapêutico , Nanopartículas/uso terapêutico , Polissacarídeos/química , Administração Oral , Alginatos/síntese química , Quitosana/química , Quitosana/uso terapêutico , Diabetes Mellitus/patologia , Sistemas de Liberação de Medicamentos , Humanos , Insulina/química , Nanopartículas/química , Polissacarídeos/uso terapêutico
11.
Curr Protoc Cell Biol ; 80(1): e53, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30126079

RESUMO

Many cell-adhesive peptides have been identified from extracellular matrix (ECM) proteins, such as collagen, fibronectin, laminin, and vitronectin. ECM proteins have various cell-adhesive sequences. Most peptides demonstrate cell-adhesive activity when simply coated on a tissue culture plate, but solubility, conformation, and coating efficiency of the peptides can significantly alter their biological function. Evaluation of peptide cell-adhesive activity using peptide-conjugated polysaccharide constructs is a useful strategy for overcoming peptide solubility and conformation problems. After a simple modification of the polysaccharides, various polysaccharides (chitosan, alginate, and hyaluronate) can fix the peptides on the tissue culture plate quantitatively. The peptide-polysaccharide strategy can be used to fix different active peptides to the polysaccharide at same time, thus, mimicking the biological functions of the ECM. This paper describes the modification of polysaccharides that are suitable for covalently coupling the peptides and evaluation of the cell-adhesive activity of peptide as a peptide-polysaccharide matrix. © 2018 by John Wiley & Sons, Inc.


Assuntos
Técnicas Citológicas/métodos , Peptídeos/farmacologia , Polissacarídeos/farmacologia , Alginatos/síntese química , Animais , Proteínas Morfogenéticas Ósseas/farmacologia , Adesão Celular/efeitos dos fármacos , Derme/citologia , Fibroblastos/citologia , Humanos , Ácido Hialurônico/síntese química , Crescimento Neuronal/efeitos dos fármacos , Células PC12 , Ratos
12.
Carbohydr Polym ; 199: 244-255, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30143127

RESUMO

Scaffolds are crucial for bone tissue engineering since their compositions and properties could significantly affect the seeded cells' behavior. In this study, we developed an interpenetrating network hydrogel by utilizing Ca2+ from calcium silicate (CS) to simultaneously crosslink silk fibroin (SF) and sodium alginate (SA). Afterwards, the hydrogels were lyophilized to obtain scaffolds and systematically evaluated by physical characterizations, in vitro cytocompatibility and alkaline phosphatase (ALP) assay. We found that CS inside the porous structure of SF/CS/SA scaffolds could remarkably enhance hydrophilicity, degradation, compression resistance, bioactivity and pH of SF/CS/SA scaffolds. Scaffolds with CS concentrations of 25% and 12% (25/CS and 12/CS) could dominantly stimulate proliferation of bone marrow stromal cells (BMSCs). Besides, BMSCs cultured with 25/CS and 12/CS scaffolds showed high ALP activity, respectively. Consequently, this study suggested SF/CS/SA scaffolds possess potential in non-loading bone tissue engineering application.


Assuntos
Alginatos/farmacologia , Materiais Biocompatíveis/farmacologia , Compostos de Cálcio/química , Fibroínas/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Silicatos/química , Tecidos Suporte/química , Alginatos/síntese química , Alginatos/química , Alginatos/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Compostos de Cálcio/síntese química , Compostos de Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Reagentes para Ligações Cruzadas/síntese química , Reagentes para Ligações Cruzadas/química , Reagentes para Ligações Cruzadas/metabolismo , Fibroínas/síntese química , Fibroínas/química , Fibroínas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Fenômenos Mecânicos , Osteogênese/efeitos dos fármacos , Porosidade , Ratos , Silicatos/síntese química , Silicatos/metabolismo , Engenharia Tecidual/métodos
13.
Mater Sci Eng C Mater Biol Appl ; 91: 190-200, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30033246

RESUMO

Degradation of the articular cartilage and structural remodeling of the subchondral bone are regarded as the two major pathological characteristics of osteoarthritis. This study aimed to investigate the effect of an interpenetrating polymer network (IPN) of a sodium hyaluronate and sodium alginate (HA/SA) scaffold combined with berberine (BER) on osteochondral repair. We first developed an IPN scaffold of HA/SA and evaluated its characteristics. Then, we analyzed the effect of the HA/SA scaffold combined with BER on the healing of osteochondral defects in vivo. Finally, we explored the mechanism of this system in osteochondral repair. The results showed that the system could simultaneously regenerate not only the cartilage but also the subchondral bone. Our results also revealed that the subchondral bone was partially repaired by activating the Wnt signaling pathway and the cartilage was protected from degeneration by the upregulation of autophagy. This study demonstrated that the combination of the IPN scaffold of HA/SA and BER is a promising strategy for the osteochondral defect regeneration.


Assuntos
Alginatos/química , Berberina/farmacologia , Regeneração Óssea/efeitos dos fármacos , Cartilagem Articular/patologia , Ácido Hialurônico/química , Polímeros/química , Tecidos Suporte/química , Alginatos/síntese química , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Cartilagem Articular/efeitos dos fármacos , Modelos Animais de Doenças , Ácido Glucurônico/síntese química , Ácido Glucurônico/química , Ácidos Hexurônicos/síntese química , Ácidos Hexurônicos/química , Ácido Hialurônico/síntese química , Polímeros/síntese química , Substâncias Protetoras/farmacologia , Coelhos , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
14.
Biomacromolecules ; 19(8): 3311-3330, 2018 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-29954171

RESUMO

A series of alginate fractions with significant differences in molecular weight and uronic acid compositions were produced by consecutive fractionation and converted to thin and strong cross-linked polymer filaments via extrusion into calcium, aluminum, or polyaluminum (PolyAl) polyvalent solutions followed by drawing and drying. Models were elaborated to relate the alginate uronic acid composition to the tensile performance in both the wet gel filament and the dry filament states. The wet gel model was compared to the theory of the unidirectional elongation of charged polyelectrolyte gels based on the classical rubber elasticity of dilated polymer networks, extended to include the contributions of non-Gaussian chain extensions and the effect of electrostatic interactions. The theory of equilibrium swelling pressure was applied to describe the observed shrinkage of the alginate gels following immersion in a polyvalent solution. Congruent with the theoretical model of charged gels, the tensile performance of the gel filaments prepared from CaCl2 depended on the compositional ratio of guluronic acid dyads in the alginate fraction multiplied by the alginate concentration, while the tensile behavior of wet gel filaments prepared by AlCl3 instead resembled that of elastic solid materials and depended only on the alginate concentration. The dry filament tensile properties were greatly dependent on the preparation conditions, particularly the ratio of stress to alginate concentration and the nature of the ions present during filament drawing. The PolyAl solution effectively caused shrinkage of alginate to a strong extent, and the resulting filaments behaved as highly stiff materials able to withstand stresses of approximately 500 MPa and having elastic moduli as high as 28 GPa.


Assuntos
Alginatos/química , Hidrogéis/química , Polimerização , Alginatos/síntese química , Reagentes para Ligações Cruzadas/química , Elasticidade , Hidrogéis/síntese química , Feófitas/química , Resistência à Tração , Molhabilidade
15.
Biosens Bioelectron ; 112: 162-169, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-29704784

RESUMO

Core/shell hydrogel microcapsules attract increasing research attention due to their potentials in tissue engineering, food engineering, and drug delivery. Current approaches for generating core/shell hydrogel microcapsules suffer from large geometric variations. Geometrically defective core/shell microcapsules need to be removed before further use. High-throughput geometric characterization of such core/shell microcapsules is therefore necessary. In this work, a continuous-flow device was developed to measure the geometric properties of microcapsules with a hydrogel shell and an aqueous core. The microcapsules were pumped through a tapered microchannel patterned with an array of interdigitated microelectrodes. The geometric parameters (the shell thickness and the diameter) were derived from the displacement profiles of the microcapsules. The results show that this approach can successfully distinguish all unencapsulated microparticles. The geometric properties of core/shell microcapsules can be determined with high accuracy. The efficacy of this method was demonstrated through a drug releasing experiment where the optimization of the electrospray process based on geometric screening can lead to controlled and extended drug releasing profiles. This method does not require high-speed optical systems, simplifying the system configuration and making it an indeed miniaturized device. The throughput of up to 584 microcapsules per minute was achieved. This study provides a powerful tool for screening core/shell hydrogel microcapsules and is expected to facilitate the applications of these microcapsules in various fields.


Assuntos
Alginatos/química , Técnicas Biossensoriais , Cápsulas/química , Hidrogéis/química , Alginatos/síntese química , Cápsulas/síntese química , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Hidrogéis/síntese química
16.
Molecules ; 23(3)2018 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-29534439

RESUMO

Hollow multilayered capsules have shown massive potential for being used in the biomedical and biotechnology fields, in applications such as cellular internalization, intracellular trafficking, drug delivery, or tissue engineering. In particular, hollow microcapsules, developed by resorting to porous calcium carbonate sacrificial templates, natural-origin building blocks and the prominent Layer-by-Layer (LbL) technology, have attracted increasing attention owing to their key features. However, these microcapsules revealed a great tendency to aggregate, which represents a major hurdle when aiming for cellular internalization and intracellular therapeutics delivery. Herein, we report the preparation of well-dispersed polysaccharide-based hollow multilayered microcapsules by combining the LbL technique with an optimized purification process. Cationic chitosan (CHT) and anionic alginate (ALG) were chosen as the marine origin polysaccharides due to their biocompatibility and structural similarity to the extracellular matrices of living tissues. Moreover, the inexpensive and highly versatile LbL technology was used to fabricate core-shell microparticles and hollow multilayered microcapsules, with precise control over their composition and physicochemical properties, by repeating the alternate deposition of both materials. The microcapsules' synthesis procedure was optimized to extensively reduce their natural aggregation tendency, as shown by the morphological analysis monitored by advanced microscopy techniques. The well-dispersed microcapsules showed an enhanced uptake by fibroblasts, opening new perspectives for cellular internalization.


Assuntos
Alginatos/síntese química , Materiais Biocompatíveis/síntese química , Quitosana/síntese química , Alginatos/química , Animais , Materiais Biocompatíveis/química , Carbonato de Cálcio , Cápsulas , Linhagem Celular , Quitosana/química , Sistemas de Liberação de Medicamentos , Ácido Glucurônico/síntese química , Ácido Glucurônico/química , Ácidos Hexurônicos/síntese química , Ácidos Hexurônicos/química , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Estrutura Molecular , Porosidade
17.
J Biomed Mater Res A ; 106(7): 1997-2006, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29569838

RESUMO

Although various biopolymers and synthetic compounds have been proposed and tested as the vitreous substitutes, no ideal material has been identified yet. In the present study, we developed an in situ-formed hydrogel by crosslinking hydroxypropyl chitosan with alginate dialdehyde. Physical properties of the hydrogel were studied and the cytotoxicity was evaluated using L929 fibroblasts, rabbit corneal endothelial cells and retinal pigment epithelial cells. In a preliminary in vivo study, the hydrogel was employed as vitreous substitute after vitrectomy surgery on rabbits and multiple parameters indicating biosafety and biocompatibility were measured and analyzed postoperatively. Our results showed that the refractive index, transmittance, pH value and density of the hydrogel were similar to those of human vitreous. Cytotoxicity tests demonstrated the hydrogel to be nontoxic to all of the three cell lines selected. Using the rabbit model, we showed that the hydrogel could form in situ and postoperative analysis of slit-lamp observation, intraocular pressure, corneal endothelium examination, B-scan ultrasound and fundus photography showed no significant adverse reactions in the operated eyes during the 90-day follow-up. However, electroretinogram and histopathological examinations indicated minor vision decline and decrease of the densities of cones and rods in the operated rabbit eyes. Collectively, our study suggested that the in situ-formed hydrogel could potentially be used as a vitreous substitute, with its long-term safety and efficacy to be further assessed. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1997-2006, 2018.


Assuntos
Organismos Aquáticos/química , Hidrogéis/farmacologia , Polissacarídeos/farmacologia , Alginatos/síntese química , Alginatos/química , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Quitosana/síntese química , Quitosana/química , Eletrorretinografia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Epitélio Posterior/efeitos dos fármacos , Epitélio Posterior/patologia , Estudos de Viabilidade , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fundo de Olho , Hidrogéis/síntese química , Hidrogéis/química , Pressão Intraocular/efeitos dos fármacos , Masculino , Camundongos , Coelhos , Epitélio Pigmentado da Retina/citologia , Reologia
18.
Acta Biomater ; 65: 53-65, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29101016

RESUMO

Alginate hydrogels have been investigated for a broad variety of medical applications. The ability to assemble hydrogels at neutral pH and mild temperatures makes alginate a popular choice for the encapsulation and delivery of cells and proteins. Alginate has been studied extensively for the delivery of islets as a treatment for type 1 diabetes. However, poor stability of the encapsulation systems after implantation remains a challenge. In this paper, alginate was modified with 2-aminoethyl methacrylate hydrochloride (AEMA) to introduce groups that can be photoactivated to generate covalent bonds. This enabled formation of dual crosslinked structure upon exposure to ultraviolet light following initial ionic crosslinking into bead structures. The degree of methacrylation was varied and in vitro stability, long term swelling, and cell viability examined. At low levels of the methacrylation, the beads could be formed by first ionic crosslinks followed by exposure to ultraviolet light to generate covalent bonds. The methacrylated alginate resulted in more stable beads and cells were viable following encapsulation. Alginate microbeads, ionic (unmodified) and dual crosslinked, were implanted into a rat omentum pouch model. Implantation was performed with a local injection of 100 µl of 50 µg/ml of Lipopolysaccharide (LPS) to stimulate a robust inflammatory challenge in vivo. Implants were retrieved at 1 and 3 weeks for analysis. The unmodified alginate microbeads had all failed by week 1, whereas the dual-crosslinked alginate microbeads remained stable up through 3 weeks. The modified alginate microbeads may provide a more stable alternative to current alginate-based systems for cell encapsulation. STATEMENT OF SIGNIFICANCE: Alginate, a naturally occurring polysaccharide, has been used for cell encapsulation to prevent graft rejection of cell transplants for people with type I diabetes. Although some success has been observed in clinical trials, the lack of reproducibility and failure to reach insulin dependence for longer periods of time indicates the need for improvements in the procedure. A major requirement for the long-term function of alginate encapsulated cells is the mechanical stability of microcapsules. Insufficient mechanical integrity of the capsules can lead to immunological reactions in the recipients. In this work, alginate was modified to allow photoactivatable groups in order to allow formation of covalent crosslinks in addition to ionic crosslinking. The dual crosslinking design prevents capsule breakdown following implantation in vivo.


Assuntos
Alginatos/síntese química , Reagentes para Ligações Cruzadas/química , Microesferas , Alginatos/química , Animais , Hidrogéis , Inflamação/induzido quimicamente , Lipopolissacarídeos/administração & dosagem , Masculino , Metacrilatos/química , Modelos Animais , Omento , Ratos , Ratos Sprague-Dawley , Raios Ultravioleta
19.
Microb Pathog ; 114: 17-24, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29138082

RESUMO

The successful treatment of multi-drug resistant microbial pathogens represents a major challenge for public health management. Here, chitosan-alginate (CS/ALG) microspheres with narrow size distribution were fabricated by ionically cross linking method using Ca2+ ions as agents for polymer solidification. The physicochemical properties of CS/ALG microspheres, such as surface morphology and size, were studied by SEM. The functional group interactions were confirmed by Fourier transform infrared (FTIR) spectroscopy. SEM revealed that the CS/ALG microspheres were spherical in shape with smooth surfaces, size was 50-100 µm. The synthesized CS/ALG microspheres showed antibacterial and antibiofilm activity on bacteria of public health relevance. CS/ALG microspheres exhibited antibacterial activity at the concentration of 5-20 µg, with significant inhibitory zones on multiple antibiotic resistant pathogens, including Gram positive Staphylococcus aureus, Enterococcus faecalis, and Gram negative Pseudomonas aeruginosa and Proteus vulgaris. Furthermore, in situ light microscopy and confocal laser scanning microscopy (CLSM) showed that CS/ALG microspheres inhibited the bacterial biofilm formation in S. aureus, E. faecalis P. aeruginosa and P. vulgaris after a single treatment with 40 µg. Overall, our findings underlined that chemically synthesized CS/ALG biomaterial has high antibacterial and antibiofilm activity against a number of microbial pathogens of interest for human health, thus this synthesis route can be further exploited for drug development in current biomedical science.


Assuntos
Alginatos/síntese química , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Quitosana/síntese química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Microesferas , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Materiais Biocompatíveis , Cálcio/química , Portadores de Fármacos/química , Enterococcus faecalis/efeitos dos fármacos , Ácido Glucurônico/síntese química , Ácidos Hexurônicos/síntese química , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Proteus vulgaris/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície
20.
Int J Biol Macromol ; 107(Pt A): 1261-1269, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28962846

RESUMO

Islet transplantation has the potential of reestablishing naturally-regulated insulin production in Type 1 diabetic patients. Nevertheless, this procedure is limited due to the low islet survival after transplantation and the lifelong immunosuppression to avoid rejection. Islet embedding within a biocompatible matrix provides mechanical protection and a physical barrier against the immune system thus, increasing islet survival. Alginate is the preferred biomaterial used for embedding insulin-producing cells because of its biocompatibility, low toxicity and ease of gelation. However, alginate gelation is poorly controlled, affecting its physicochemical properties as an injectable biomaterial. Including different concentrations of the phosphate salt Na2HPO4 in alginate hydrogels, we can modulate their gelation time, tuning their physicochemical properties like stiffness and porosity while maintaining an appropriate injectability. Moreover, these hydrogels showed good biocompatibility when embedding a rat insulinoma cell line, especially at low Na2HPO4 concentrations, indicating that these hydrogels have potential as injectable biomaterials for Type 1 Diabetes Mellitus treatment.


Assuntos
Alginatos/química , Terapia Baseada em Transplante de Células e Tecidos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Alginatos/síntese química , Alginatos/uso terapêutico , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Diabetes Mellitus Tipo 1/patologia , Ácido Glucurônico/síntese química , Ácido Glucurônico/química , Ácido Glucurônico/uso terapêutico , Ácidos Hexurônicos/síntese química , Ácidos Hexurônicos/química , Ácidos Hexurônicos/uso terapêutico , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/uso terapêutico , Insulina/biossíntese , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Ratos
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