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1.
Carbohydr Res ; 500: 108218, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33358143

RESUMO

Reactive oxygen species (ROS), induced by medical and life irradiation, have led to diverse diseases. Natural antioxidants (NAs) have been widely used to protect the body from the harmful effects of ROS. NAs have biocompatible properties but their bioavailability in the body is very low. This article discusses possible solutions to improve the bioavailability using several preparation and encapsulation techniques for microspheres using chitosan as a carrier. The first is the emulsion technique that controls particle size (0.5-1000 µm) according to the speed (RPM) of the agitator. The second technique discussed is spray drying-a very simple method that can control particle size (5-5000 µm) according to the nozzle size and discharge pressure. The third is the extrusion technique, which can control particle size (250-2500 µm) according to the syringe pore size. These techniques have enormous potential for use as drug delivery systems (DDS) in the functional food and biomedical field industries.


Assuntos
Antioxidantes/farmacocinética , Produtos Biológicos/farmacocinética , Quitosana/síntese química , Microesferas , Antioxidantes/química , Disponibilidade Biológica , Produtos Biológicos/química , Células CACO-2 , Configuração de Carboidratos , Quitosana/química , Humanos , Absorção Intestinal/efeitos dos fármacos
2.
Carbohydr Polym ; 209: 161-171, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30732795

RESUMO

To develop a carrier for targeted drug delivery and triggered drug release in a reducing-tumor environment, reduction-sensitive hyaluronic acid-g-stearic acid (HCS) micelles were synthesized using a coupling agent. The HCS 40% was shown to have a more compact particle size than HCS 20% and the particle size of doxorubicin (DOX)-loaded HCS (HCSD) was increased relative to that of HCS micelles. The behavior of DOX release from HCSD showed that DOX was rapidly released in GSH (10 mM) solution. The site-specific targeting effect of HCSD nanoparticles was investigated by cellular uptake and competition assay at HCT116 and CT26 cell lines. An in vivo study of HCSD revealed that tumor suppression and site-specific targeted delivery of HCSD nanoparticles in HCT116-xenografted tumors were more superb than in the CT26-xenografted tumor. These results suggest that HCSD nanoparticles can be expected to have high therapeutic efficacy because they enable targeted drug delivery and rapid drug release.


Assuntos
Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ácido Hialurônico/química , Micelas , Ácidos Esteáricos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Glutationa/química , Células HCT116 , Humanos , Camundongos , Nanopartículas/química , Oxirredução
3.
J Nanosci Nanotechnol ; 19(4): 2329-2333, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30486993

RESUMO

In this work, we prepared basalt based nanostructured zeolite 13X by alkali fusion and hydrothermal synthesis process. The sample prepared was characterized using XRD, SEM, and low-temperature nitrogen analysis. The adsorption equilibrium and kinetic characteristics of ammonia nitrogen (NH+4-N) and phosphate phosphorus (PO3-4-P) were investigated. It was found that the basalt based nanostructured zeolite 13X showed high adsorption capacities for NH+4-N (75 mg/g) and PO3-4-P (25 mg/g) under the experimental conditions used. Our results demonstrate that basalt based zeolite 13X can be a good alternative adsorbent for the simultaneously removal of NH+4-N and PO3-4-P from aqueous solution.

4.
Int J Biol Macromol ; 121: 301-308, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30312696

RESUMO

This study demonstrated the anti-adhesion and wound healing effect of a visible light curable anti-adhesion agent using an alginate derivative modified with a furfuryl moiety. Visible light-curable furfuryl alginate (F-Alg) was prepared in conjugation with alginate and furfurylamine by an amide coupling reaction, and the conjugated F-Alg was characterized by 1H NMR analysis. The cytotoxicity, cell adhesion, and cell permeability of the F-Alg were evaluated for use in anti-adhesion applications. Drug immobilization and protein release were assessed to verify whether the alginate derivatives and drugs were photo-immobilized. In in vivo anti-adhesion testing, the new anti-adhesion agent prepared in this study acted as a physical protective layer by forming a biofilm on the surgical site. Additionally, along with gradual decomposition of the photo-crosslinked alginate derivative, the immobilized drug was released, and additional effects such as accelerated wound healing are expected. Thus, visible light-curable F-Alg has good application potential as an anti-adhesion agent.


Assuntos
Alginatos/química , Alginatos/farmacologia , Furanos/química , Luz , Animais , Bovinos , Adesão Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Camundongos , Células NIH 3T3 , Soroalbumina Bovina/química , Cicatrização/efeitos dos fármacos
5.
Int J Biol Macromol ; 120(Pt A): 915-920, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30071230

RESUMO

Recently, many of studies have been attempted to determine how to decrease adhesion. To effectively prevent adhesion, decrease in unnecessary surgical procedures, prevention of contact with other tissue, and drug treatment for inflammation are required. However, current anti-adhesion materials have disadvantages. To solve current problems, we prepared a biocompatible drug-loaded anti-adhesion barrier using a visible-light curable furfuryl gelatin derivative. We used riboflavin as a photo-initiator in the photo-curing process. The biocompatibility of riboflavin was estimated compared with that of Rose Bengal. In addition, the curing ratio was measured to determine whether riboflavin initiated photo-curing. We also evaluated the curing ratio of riboflavin according to the concentration of F-gelatin and the photo-irradiation time. A drug used to decrease inflammation that causes adhesion should not disappear from the surgical site and should also be released consistently. For this, we observed the release profiles of photo-immobilized ibuprofen with different concentrations of F-gelatin. Because an anti-adhesion barrier should protect from bacterial infection we evaluated the protective ability of a barrier formed by F-gelatin. In conclusion, a drug-loaded anti-adhesion barrier was prepared using a visible-light curable furfuryl gelatin derivative, with riboflavin as a photo-initiator. We expect that this drug-loaded anti-adhesion barrier effectively decrease adhesion formation.


Assuntos
Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Gelatina/farmacologia , Inflamação/tratamento farmacológico , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos da radiação , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Portadores de Fármacos/efeitos da radiação , Gelatina/química , Humanos , Luz , Riboflavina/química , Rosa Bengala/química , Rosa Bengala/efeitos da radiação
6.
J Pharm Sci ; 107(10): 2702-2712, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29936202

RESUMO

Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H2O2, resulting in an increase of particle size and in a size distribution having multimodal pattern. PL release increased under acidic conditions and in the presence of H2O2. Uptake of ChitoPEGse nanoparticles by CT26 cells significantly increased in acidic and redox state. PL-incorporated ChitoPEGse nanoparticles (PL NPs) showed similar anticancer activity in vitro against A549 and CT26 cells compared to PL itself. PL NP showed superior anticancer and antimetastatic activity in an in vivo CT26 cell pulmonary metastasis mouse model. Furthermore, an immunofluorescence imaging study demonstrated that PL NP conjugates were specifically delivered to the tumor mass in the lung. Conclusively, ChitoPEGse nanoparticles were able to be delivered to cancer cells with an acidic- or redox state-sensitive manner and then efficiently targeted pulmonary metastasis of cancer cells since ChitoPEGse nanoparticles have dual pH- and redox-responsiveness.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Dioxolanos/química , Dioxolanos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/administração & dosagem , Nanopartículas/química , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Quitosana/análogos & derivados , Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Concentração de Íons de Hidrogênio , Oxirredução , Polietilenoglicóis/química
7.
Int J Biol Macromol ; 115: 459-468, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29680502

RESUMO

Branched polyethylenimine (bPEI) was well known as high transfection agent, which has many amine group. However, utilization of bPEI was limited due to high toxicity. To solve these problems, bPEI was introduced to low molecular weight water-soluble chitosan (LMWSC) with coupling agent. In addition, hyaluronic acid (HA), one of natural anion polymer, was introduced to binary complex of pDNA/bPEI-grafted LMWSC (LMPEI) to target the specific cancer cell and impart the serum resistant. Ternary complexes of pDNA/LMPEI/HA were prepared by electrostatic charge interaction and their binding affinity and DNase protection assay were conducted by gel retardation assay. Particle size of ternary complexes showed that had each 482 ±â€¯245.4 (pDNA/LMPEI2%/HA, 1:16:1, w/w/w) and 410 ±â€¯78.5 nm (pDNA/LMPEI4%/HA, 1:16:2, w/w/w). Moreover, to demonstrate serum-resistant effect of ternary complexes, particle size of them was measured according to incubated time (0-10 h) under serum condition. Transfection assay of ternary complexes showed that their transfection efficiency in CD44-receptor overexpressed HCT116 cell was higher than CD44-receptor negative CT26 cell. Additionally, intracellular uptake of ternary complexes with propidium iodide (PI)-labeled pDNA was observed to confirm targeting effect and cellular internalization by fluorescence microscopy. These results suggest that ternary complexes are superb gene carrier with excellent serum-resistant and high gene transfection.


Assuntos
Portadores de Fármacos/química , Técnicas de Transferência de Genes , Ácido Hialurônico/química , Soro/metabolismo , Quitosana/química , Células HCT116 , Células HEK293 , Humanos , Espaço Intracelular/metabolismo , Tamanho da Partícula , Plasmídeos/genética , Polietilenoimina/química , Solubilidade , Água/química
8.
Carbohydr Polym ; 178: 322-330, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29050600

RESUMO

For efficient gene delivery, non-viral vectors should have high cellular uptake, excellent endosomal escape, and the ability to rapidly release the gene into the cytoplasm. Here, we developed a disulfide bond-conjugated bioreducible LMWSC-g-bPEI (LCP) composed of low molecular-weight water soluble chitosan (LMWSC), bPEI, and cystamine (Cys). The developed LCP had advantages such as low toxicity, great endosomal escape, and rapid release of pDNA into the cytoplasm. The polyplexes with LCP showed higher uptake into the nucleus and greater transfection efficiency than that without disulfide bond. Moreover, LCP polymer and polyplexes with LCP indicated lower cytotoxicity than bPEI 25kDa. In addition, a gel retardation assay and particle size were analyzed to demonstrate the reduction-sensitive gene delivery system. Besides, intracellular uptake pathway of polyplexes was investigated by various endocytosis inhibitor and confirmed to internalization into cell via macropinocytosis. These results suggest that bioreducible LCP is a superb non-viral vector for efficient gene delivery.


Assuntos
Quitosana/química , Vetores Genéticos/química , Polietilenoimina/química , Transfecção , DNA , Dissulfetos , Células HCT116 , Células HEK293 , Humanos , Peso Molecular , Água
9.
Int J Pharm ; 532(1): 194-203, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-28888976

RESUMO

The polysaccharide chitosan has abundant cationic amine groups, and can form ion-complexes with anionic molecules such as the strong photosensitizer chlorin e6 (Ce6). In this study, water-soluble chitosan (WSC) was used to fabricate Ce6-incorporated nanophotosensitizers (Abbreviated as ChitoCe6 nanophotosensitizer) via a self-assembling process. This was accomplished by dissolving WSC in pure water and then directly mixing the solution with solid Ce6 causing ion complex formation between WSC and Ce6. The resulting nanophotosensitizer was spherical in shape and had a particle size of less than 300nm. The photodynamic effect of ChitoCe6 nanophotosensitizer was evaluated using gastrointestinal (GI) cancer cells. At in vitro study using SNU478 cholangiocarcinoma cells, ChitoCe6 nanophotosensitizer showed improved Ce6 uptake by tumor cells, reactive oxygen species production, and cellular phototoxicity. An in vivo study using SNU478-bearing nude mice showed that the ChitoCe6 nanophotosensitizer efficiently accumulated in the tumor tissue and inhibited tumor growth more than treatment with Ce6 alone. Furthermore, ChitoCe6 nanophotosensitizer was also efficiently absorbed through tissue layers in an ex vivo study using porcine bile duct explants. ChitoCe6 nanophotosensitizer showed enhanced photosensitivity and photodynamic effects against cancer cells in vitro and in vivo. We present ChitoCe6 nanophotosensitizer as a promising candidate for photodynamic therapy of GI cancer.


Assuntos
Quitosana/administração & dosagem , Nanopartículas/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Quitosana/uso terapêutico , Clorofilídeos , Humanos , Luz , Masculino , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Solubilidade , Carga Tumoral/efeitos dos fármacos , Água/química
10.
Environ Toxicol Pharmacol ; 48: 22-30, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27716532

RESUMO

Inflammatory diseases have become one of the leading causes of health issue throughout the world, having a considerable influence on healthcare costs. With the emerging developments in natural product, synthetic and combinatorial chemistry, a notable success has been achieved in discovering natural products and their synthetic structural analogs with anti-inflammatory activity. However, many of these therapeutics have indicated detrimental side effects upon prolonged usage. Marine algae have been identified as an underexplored reservoir of unique anti-inflammatory compounds. These include polyphenols, sulfated polysaccharides, terpenes, fatty acids, proteins and several other bioactives. Consumption of these marine algae could provide defense against the pathophysiology of many chronic inflammatory diseases. With further investigation, algal anti-inflammatory phytochemicals have the potential to be used as therapeutics or in the synthesis of structural analogs with profound anti-inflammatory activity with reduced side effects. The current review summarizes the latest knowledge about the potential anti-inflammatory compounds discovered from marine algae.


Assuntos
Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Feófitas/química , Rodófitas/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Células Cultivadas , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Estrutura Molecular , Feófitas/crescimento & desenvolvimento , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Rodófitas/crescimento & desenvolvimento , Água do Mar , Terpenos/isolamento & purificação , Terpenos/farmacologia
11.
Carbohydr Polym ; 153: 512-517, 2016 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-27561523

RESUMO

This study describes a simple preparation of functional polysaccharides from Pyropia yezoensis using a microwave-assistant rapid enzyme digest system (MAREDS) with various carbohydrases, and evaluates their antioxidative effects. Polysaccharide hydrolysates were prepared using MAREDS under different hydrolytic conditions of the carbohydrases and microwave powers. Polysaccharides less than 10kDa (Low molecular weight polysaccharides, LMWP, ≤10kDa) were efficiently obtained using an ultrafiltration (molecular weight cut-off of 10kDa). MAREDS increases AMG activation via an increased degree of hydrolysis; the best AMG hydrolysate was prepared using a 10:1 ratio of substrate to enzyme for 2h in MAREDS with 400W. LMWP consisted of galactose (27.3%), glucose (64.5%), and mannose (8.3%) from the AMG hydrolysate had stronger antioxidant effects than the high molecular weight polysaccharides (>10kDa). We rapidly prepared functional LMWPs by using MAREDS with carbohydrases, and suggest that LMWP might be potentially a valuable algal polysaccharide antioxidant.


Assuntos
Antioxidantes/química , Polissacarídeos/química , Rodófitas/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Fracionamento Químico , Micro-Ondas , Monossacarídeos/química , Monossacarídeos/isolamento & purificação , Monossacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Ultrafiltração
12.
J Nanosci Nanotechnol ; 16(5): 4638-42, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27483803

RESUMO

The catalytic oxidation of toluene was carried out to investigate the effect of the support on the properties and performance of a supported palladium catalyst (1 wt% loading). γ-Al2O3), SiO2 and TiO2 were used as supports. The properties of the prepared catalysts were characterized by XRD, BET, PT, TPD, TPR, XPS and FE-TEM analyses. The experimental results showed that the order of catalytic performance was 1 wt% Pd/TiO2 > 1 wt% Pd/SiO2 > 1 wt% Pd/γ-Al2O3. A strong interaction between the palladium and support was found, which affected the palladium surface concentration and particle size. The higher catalytic activity of the Pd/TiO2 catalyst was attributed to the higher palladium surface concentration and larger particle size.

13.
Int J Biol Macromol ; 91: 804-11, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27296444

RESUMO

The aim of this study was to analyze antioxidant properties of a polysaccharide isolated from Psidium guajava leaves (PS-PGL) in vitro including its radical scavenging activities and protective effects against damage to cells as well as in vivo in zebrafish. The water extract of P. guajava leaves (WE-PGL) and PS-PGL showed strong radical scavenging effects in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, and alkyl radical. Compared to WE-PGL, PS-PGL enhanced all scavenging activities and in particular strongly scavenged the hydroxyl radical (50% inhibitory concentration [IC50], 0.02mg/mL). In addition, PS-PGL exerted a protective effect against hydrogen peroxide-induced oxidative stress and against toxicity to Vero cells. Furthermore, in vivo experiments using zebrafish embryos indicated that treatment with hydrogen peroxide decreased the survival rate and heart-beating rate of zebrafish embryos, whereas these problems were reduced by PS-PGL treatment. Moreover, PS-PGL inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production, lipid peroxidation, and cell death. Taken together, these results suggest that PS-PGL may be useful as a beneficial antioxidant material in the food and cosmetic industries.


Assuntos
Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/química , Polissacarídeos/farmacologia , Psidium/química , Animais , Antioxidantes/química , Chlorocebus aethiops , Oxirredutases/metabolismo , Polissacarídeos/química , Espécies Reativas de Oxigênio/metabolismo , Células Vero
14.
J Mater Sci Mater Med ; 27(4): 66, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26886814

RESUMO

The aim of this study was to evaluate antiproliferative sirolimus- and antioxidative alpha-lipoic acid (ALA)-eluting stents using biodegradable polymer [poly-L-lactic acid (PLA)] in a porcine coronary overstretch restenosis model. Forty coronary arteries of 20 pigs were randomized into four groups in which the coronary arteries had a bare metal stent (BMS, n = 10), ALA-eluting stent with PLA (AES, n = 10), sirolimus-eluting stent with PLA (SES, n = 10), or sirolimus- and ALA-eluting stent with PLA (SAS, n = 10). A histopathological analysis was performed 28 days after the stenting. The ALA and sirolimus released slowly over 30 days. There were no significant differences between groups in the injury or inflammation score; however, there were significant differences in the percent area of stenosis (56.2 ± 11.78% in BMS vs. 51.5 ± 12.20% in AES vs. 34.7 ± 7.23% in SES vs. 28.7 ± 7.30% in SAS, P < 0.0001) and fibrin score [1.0 (range 1.0-1.0) in BMS vs. 1.0 (range 1.0-1.0) in AES vs. 2.0 (range 2.0-2.0) in SES vs. 2.0 (range 2.0-2.0) in SAS, P < 0.0001] between the four groups. The percent area of stenosis based on micro-computed tomography corresponded with the restenosis rates based on histopathological stenosis in different proportions in the four groups (54.8 ± 7.88% in BMS vs. 50.4 ± 14.87% in AES vs. 34.5 ± 7.22% in SES vs. 28.9 ± 7.22% in SAS, P < 0.05). SAS showed a better neointimal inhibitory effect than BMS, AES, and SES at 1 month after stenting in a porcine coronary restenosis model. Therefore, SAS with PLA can be a useful drug combination for coronary stent coating to suppress neointimal hyperplasia.


Assuntos
Reestenose Coronária/terapia , Stents Farmacológicos , Sirolimo/farmacologia , Ácido Tióctico/farmacologia , Animais , Fibroblastos , Ratos , Sirolimo/química , Suínos , Ácido Tióctico/química , Resultado do Tratamento
15.
J Control Release ; 221: 37-47, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26639177

RESUMO

Reactive oxygen species (ROS) produced by host phagocytes exert antibacterial action against a variety of pathogens and ROS-induced oxidative stress is the governing mechanism for the antibacterial activity of major bactericidal antibiotics. In particular, hydroxyl radical is a strong and nonselective oxidant which can damage biomolecules such as DNA, proteins and lipids. Ferrous ion is known to convert mild oxidant hydrogen peroxide (H2O2) into highly reactive and toxic hydroxyl radicals, referred to as Fenton reaction. Herein, we report a new class of antibacterial agents based on Fenton reaction-performing nanostructures, composed of H2O2-generating polymer (PCAE) and iron-containing ferrocene. Amphiphilic PCAE was designed to incorporate H2O2-generating cinnamaldehyde through acid-cleavable linkages and self-assemble to form thermodynamically stable micelles which could encapsulate ferrocene in their hydrophobic core. All the experiments in vitro display that ferrocene-loaded PCAE micelles produce hydroxyl radicals to kill Escherichia coli and Pseudomonas aeruginosa through membrane damages. Intraperitoneally injected ferrocene-loaded PCAE micelles significantly reduced the lung damages and therefore increased the survival rate of mice infected with drug resistant P. aeruginosa. Given their potent antibacterial activity, ferrocene-loaded PCAE micelles hold great potential as a new class of ROS-manipulating antibacterial agents.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/uso terapêutico , Compostos Ferrosos/uso terapêutico , Peróxido de Hidrogênio/metabolismo , Ferro/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Acroleína/administração & dosagem , Acroleína/química , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Humanos , Radical Hidroxila/metabolismo , Metalocenos , Camundongos , Camundongos Endogâmicos ICR , Micelas , Espécies Reativas de Oxigênio/metabolismo
16.
Carbohydr Polym ; 135: 153-61, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26453863

RESUMO

In this study, we designed a novel carrier which was having low cytotoxicity, site-specific target function, and high transfection efficiency using low molecular weight water soluble O-carboxymethyl chitosan (OCMCh), branched low molecular weight poly(ethyleneimine) (bPEI), and targeting ligand (epitope type, HER-2/neu). OCMCh/bPEI/targeting ligand, HPOCP copolymer, and targeting ligand-modified polyamphoteric polymer, and were prepared by chemical reaction and characterized by (1)H NMR and FT-IR. The binding affinity, protecting efficiency, and releasing ability of gene/HPOCP polyplex were confirmed by gel retardation assay. The pDNA(pEGFP)/HPOCP polyplexes showed high gene transfection efficiency in HCT 119 cell. In addition, siRNA/HPOCP polyplexes formed spherical shape and have particle sizes from 100 to 300nm. The siRNA/HPOCP polyplexes have lower cytotoxicity than PEI in the all of siRNA concentrations ranging from 0 to 2µg/µL in HEK 293 cells. The cell viability of siRNA/HPOCP polyplexes was performed in SK-Br3 cells with VEGF siRNA or BCL2 siRNA. In addition, confocal laser-scanning microscopy and flow cytometry assay were performed for cellular localization and cellular uptake efficiency of siRNA/HPOCP polyplexes. The results of the present study demonstrate that HPOCP copolymer is a good candidate as gene delivery carriers for gene delivery system or gene therapy.


Assuntos
Quitosana/análogos & derivados , DNA/administração & dosagem , Técnicas de Transferência de Genes , Polietilenoimina/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Receptor ErbB-2/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Quitosana/administração & dosagem , Quitosana/química , DNA/química , Terapia Genética , Humanos , Neoplasias/genética , Neoplasias/terapia , Plasmídeos , Polietilenoimina/química , RNA Interferente Pequeno/química
17.
J Mech Behav Biomed Mater ; 53: 68-77, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26318568

RESUMO

In this study, we aimed to evaluate the mechanical effects of different stent linker designs on in-stent restenosis in porcine coronary arteries. We fabricated stents with an open-cell structure composed of nine main cells and three linker structures in model 1 (I-type), model 2 (S-types) and model 3 (U-types)) as well as Model 4, which is similar to a commercial bare metal stent design. The stent cells were 70 mm thick and wide, with a common symmetrical wave pattern. As the radial force increased, the number of main cells increased and the length of linker decreased. Radial force was higher in model 1, with a linear I-linker, than in models with S- or U-linkers. The flexibility measured by three-point bending showed a force of 1.09 N in model 1, 0.35 N in model 2, 0.19 N in model 3, and 0.31 N in model 4. The recoil results were similar in all models except model 4 and were related to the shape of the main cells. The foreshortening results were related to linker shape, with the lowest foreshortening observed in model 3 (U-linker). Restenosis areas in the porcine restenosis model 4 weeks after implantation were 35.4 ± 8.39% (model 1), 30.4 ± 7.56% (model 2), 40.6 ± 9.87% (model 3) and 45.1 ± 12.33% (model 4). In-stent restenosis rates measured by intravascular ultrasound (IVUS) and micro-computed tomography (micro-CT) showed similar trends as percent area stenosis measured by micro-CT. Model 2, with optimized flexibility and radial force due to its S-linker, showed significantly reduced restenosis in the animal model compared to stents with different linker designs. These results suggest that the optimal stent structure has a minimum radial force for vascular support and maximum flexibility for vascular conformability. The importance of the effects of these differences in stent design and their potential relationship with restenosis remains to be determined.


Assuntos
Reestenose Coronária , Fenômenos Mecânicos , Stents , Animais , Reestenose Coronária/patologia , Vasos Coronários , Modelos Animais de Doenças , Desenho de Prótese , Segurança , Stents/efeitos adversos , Suínos
18.
Colloids Surf B Biointerfaces ; 133: 254-62, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26117805

RESUMO

In this study, we report the development of a novel, redox-sensitive chitosan-based targeted drug delivery system, containing two drugs. We determined whether the synthesized polymeric micelles (HPTOC-DOX) were suitable as a drug carrier. The formation of HPTOC-DOX micelles was confirmed by (1)H NMR. HPTOC-DOX formed micelles of approximately 151.9-311.2nm in size in aqueous solution. Analysis of the drug release profile of HPTOC-DOX in different pH conditions (pH 5.2, 6.2, and 7.4) indicated that DOX was released from HPTOC-DOX micelles at acidic pH (5.2 or 6.2), while almost no DOX was released at pH 7.4. In vitro cell cytotoxicity and hemolysis assays indicated that HPTOC-DOX micelles safely deliver anti-cancer drugs and decrease the cytotoxicity of DOX. In vitro anti-cancer activity assays, confocal laser scanning microscopy analysis of SK-BR-3 cells, and in vivo anti-tumor activity in SK-BR-3-derived tumor-bearing mice were used to evaluate synergistic drug effects and the effect of the targeting peptide (anti-human epidermal growth factor receptor 2 [HER2] target peptide, epitope form; LTVSPWY) on receptor-mediated endocytosis.


Assuntos
Quitosana/química , Doxorrubicina/administração & dosagem , Micelas , Neoplasias/tratamento farmacológico , Polímeros/química , Tocoferóis/administração & dosagem , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Células HEK293 , Humanos , Técnicas In Vitro
19.
Mol Pharm ; 12(7): 2352-64, 2015 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-26029979

RESUMO

To increase cellular uptake and endosomal escape efficiency, various methods have been studied to efficiently deliver plasmid DNA (pDNA) into the cell. Here, we designed a histidylated arginine-grafted bioreducible polymer (HABP) as a nonviral gene carrier using different ratios of histidine and arginine-grafted bioreducible poly(cystaminebis(acrylamide)-diaminohexane) (poly(CBA-DAH)), known as ABP, to increase cellular uptake and endosomal escape efficiency. HABPs consist of arginine (cell penetrating functionality), histidine (endosome buffering functionality), and a disulfide bond backbone (bioreducible functionality in cytoplasm). These components result in the following: (1) polyplexes are easily taken up by cells, (2) polyplexes can easily escape from the endosome into the cytosol, and (3) pDNA can dissociate from polyplexes in reducing environments such as the cytoplasm. HABPs showed increased buffering capacity over histidine-ungrafted ABP, and HABPs formed nanosized polyplexes with pDNA. These polyplexes were about 90 nm in size and had positive charges of about of 30-40 mV. HABPs/pDNA polyplexes showed enhanced transfection efficiency and no significant cytotoxicity in comparison with polyethylenimine 25 kDa (PEI 25k), histidine-ungrafted ABP, and Lipofectamine (commercial reagent) in human cervical carcinoma (HeLa), rat cardiomyocytes (H9C2), and colon carcinoma (CT26) cells.


Assuntos
Arginina/química , Histidina/química , Poliaminas/química , DNA/genética , Endossomos/metabolismo , Técnicas de Transferência de Genes , Células HeLa , Humanos , Tamanho da Partícula , Plasmídeos/genética , Transfecção/métodos
20.
J Control Release ; 209: 179-85, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-25937533

RESUMO

Small interfering ribonucleic acid (siRNA), 20-25 base pairs in length, can interfere with the expression of specific genes. Recently, many groups reported the therapeutic intervention of siRNA in various cancer cells. In this study, dendrimer type bio-reducible polymer (PAM-ABP) which was synthesized using arginine grafted bio-reducible poly(cystaminebisacrylamide-diaminohexane) (ABP) and polyamidoamine (PAMAM) was used to deliver anti-VEGF siRNA into cancer cell lines including human hepatocarcinoma (Huh-7), human lung adenocarcinoma (A549), and human fibrosarcoma (HT1080) cells and access their potential as a siRNA delivery carrier for cancer therapy. PAM-ABP and siRNA formed polyplexes with average diameter of 116 nm and charge of around +24.6 mV. The siRNA in the PAM-ABP/siRNA polyplex was released by 5mM DTT and heparin. VEGF gene silencing efficiency of PAM-ABP/siRNA polyplexes was shown to be more effective than PEI/siRNA polyplexes in three cell lines with the following order HT1080>A549>Huh-7.


Assuntos
Dendrímeros/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/química , Dendrímeros/farmacologia , Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias/terapia , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia
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