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1.
Chem Commun (Camb) ; 55(60): 8876-8879, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31286121

RESUMO

Here we report template-free synthesis of imine-linked calix[4]arene hollow nanocapsules and their utility in the effective delivery of a poorly soluble cancer drug into tumor cells. These stimuli-responsive nanocapsules show high drug loading and release which resulted in a 40-fold higher cytotoxicity for breast cancer cell line over normal cells.


Assuntos
Antineoplásicos/farmacologia , Calixarenos/química , Camptotecina/farmacologia , Portadores de Fármacos/química , Nanocápsulas/química , Fenóis/química , Antineoplásicos/química , Calixarenos/síntese química , Calixarenos/toxicidade , Camptotecina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Nanocápsulas/toxicidade , Fenóis/síntese química , Fenóis/toxicidade
2.
Chem Commun (Camb) ; 55(61): 9039-9042, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292589
3.
Chem Commun (Camb) ; 55(58): 8434-8437, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31259350

RESUMO

Phosphatidylcholine is the main component of liposomes and other phospholipid-based nanocarriers in drug delivery. However, the functions and applications of these nanocarriers are extremely limited by conventional phospholipids. Here we report novel disulfide phosphatidylcholines (SS-PCs) and SS-PC based liposomes (SS-LPs) used as alternatives to traditional phospholipids and liposomes.


Assuntos
Dissulfetos/química , Portadores de Fármacos/química , Lipossomos/química , Fosfatidilcolinas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Dissulfetos/síntese química , Dissulfetos/metabolismo , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Humanos , Lipossomos/síntese química , Lipossomos/metabolismo , Camundongos , Oxirredução , Fosfatidilcolinas/síntese química , Fosfatidilcolinas/metabolismo
4.
Chem Commun (Camb) ; 55(65): 9709-9712, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31353371

RESUMO

We functionalize nucleic acid nanostructures with click chemistry (for attachment of cargos) and a photocleavable linker (for release). We demonstrate cargo attachment using a fluorescein dye and release using UV trigger from an RNA three-way junction, a DNA star motif and a DNA tetrahedron. Such multifunctional nucleic acid nanostructures have potential in targeted drug delivery.


Assuntos
DNA/química , Portadores de Fármacos/química , Fluoresceínas/química , Corantes Fluorescentes/química , Nanoestruturas/química , RNA/química , Animais , Fagos Bacilares/genética , Sequência de Bases , Bovinos , Química Click , DNA/sangue , DNA/síntese química , DNA/efeitos da radiação , Portadores de Fármacos/síntese química , Portadores de Fármacos/efeitos da radiação , Fluorescência , Nanoestruturas/efeitos da radiação , Conformação de Ácido Nucleico , RNA/sangue , RNA/síntese química , RNA/efeitos da radiação , Raios Ultravioleta
7.
J Photochem Photobiol B ; 197: 111510, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31163288

RESUMO

Treatment of chronic lung infection becomes a great challenge due to the drug resistant bacteria. In this scenario, evolving a new drug based on lipid metal conjugation loaded with potential antibiotic provides better drug delivery. In this study, ciprofloxacin loaded selenium-lipid nanoparticle (CxLSENPs) is produced in a novel route and its antimicrobial properties were tested against clinically important Gram-negative P. aeruginosa. The synthesized CxLSENPs was characterized by biophysical techniques (UV, Fluorescence spectroscopy, Raman spectroscopy, FTIR, FESEM, HRTEM and Zeta potential). Raman spectra coupled with FTIR spectra confirmed the possible interaction of lipid components in the NPs. HRTEM analysis confirmed the spherical shape of NPs. CxLSENPs recorded greater antibacterial effects on P. aeruginosa. A drastic reduction in the count of P. aeruginosa was observed after treatment with CxLSENPs. In order to further confirm the antibacterial efficiency, the live/dead cell assay was carried out. Live/dead analysis helps us to investigate the viability of bacterial cells. The number of dead bacterial cells was significantly higher in CxLSENPs treated groups when compare to the control. Furthermore, CxLSENPs increased the antioxidant enzyme activities (SOD, GPx, CAT and LPO) in mouse and protected the liver damage from bacterial infection. This study concludes that the developed CxLSENPs might be employed as strong antimicrobial and antioxidant agents for treating lung infection or interstitial lung diseases.


Assuntos
Antibacterianos/química , Ciprofloxacino/química , Portadores de Fármacos/síntese química , Lipídeos/química , Nanopartículas/química , Selênio/química , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antioxidantes/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Catalase/metabolismo , Ciprofloxacino/farmacologia , Ciprofloxacino/uso terapêutico , Portadores de Fármacos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/microbiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Camundongos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Superóxido Dismutase/metabolismo
8.
AAPS PharmSciTech ; 20(5): 210, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161269

RESUMO

Dorzolamide HCl (DRZ) ophthalmic drop is one of the most common glaucoma medications which rapidly eliminates after instillation leading to short residence time of the drug on cornea. The purpose of the present study is to develop a pH-triggered in situ gel system for ophthalmic delivery of DRZ for treatment of ocular hypertension. In this study, a 32 full factorial design was used for preparation of in situ gel formulations using different levels of Carbopol® and hydroxyl propyl methyl cellulose (HPMC). Rheological behavior, in vitro drug release, ex vivo corneal permeability, and IOP-lowering activity were investigated. DRZ solution (2% w/v) containing of 0.1% (w/v) Carbopol® and 0.1% (w/v) HPMC was selected as the optimal formulation considering its free flow under non-physiological conditions (initial pH and 25 ± 2°C) and transition to appropriate gel form under physiological circumstance (pH 7.4 and 34°C). This in situ gel presented the mucoadhesive property. Ex vivo corneal permeability of this combined solution was similar to those of DRZ solution. The developed formulation compared to the marketed drop (Biosopt®) and DRZ 2% solution had a better performance in intraocular pressure activity. The efficiency and long duration of IOP reduction could be due to the prolonged residence time of the in situ gel. The presence of Carbopol® as a pH triggered and mucoadhesive polymer causes to attach to the ocular mucosal surface for a long term.


Assuntos
Resinas Acrílicas/farmacocinética , Anti-Hipertensivos/farmacocinética , Portadores de Fármacos/farmacocinética , Derivados da Hipromelose/farmacocinética , Sulfonamidas/farmacocinética , Tiofenos/farmacocinética , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/síntese química , Administração Oftálmica , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/síntese química , Córnea/efeitos dos fármacos , Córnea/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Liberação Controlada de Fármacos , Géis , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Concentração de Íons de Hidrogênio , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/síntese química , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Masculino , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/síntese química , Soluções Oftálmicas/farmacocinética , Coelhos , Sulfonamidas/administração & dosagem , Sulfonamidas/síntese química , Suínos , Tiofenos/administração & dosagem , Tiofenos/síntese química
9.
Ultrason Sonochem ; 55: 86-95, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084795

RESUMO

Delivery of drugs and active agents to human skin by formulation containing nanosystems have shown remarkable advance in recent nanotechnology research. The aim of current investigation is to study protein drug, extracted from medicinal leech tissue and evaluate an isotropic and kinetically stable nanoemulsion formulation, with least surfactant and co-surfactant concentrations also with optimal solubility and stability, for topical delivery. It is a fact that physical properties of oil phase has an impact on nanoemulsion formation and stabilization. In this research, various factors, such as oil types (olive oil and sesame oil) and oil content for their effects on particle size and stability of protein nanoemulsion were first investigated. Secondly, optimized formulation of protein nanoemulsion was characterized by droplet size and zeta potential analysis, Transmission electron microscopy (TEM), viscosity, pH, and refractive index. Thirdly, stability studies were done to select the best formulation. The results of our experiments showed that an increase in the concentration of olive oil and sesame oil led to a nanoemulsion with smaller size of droplets and with higher stability, respectively. However; slight variations in droplet size were observed in case of nanoemulsion with olive oil. As a result of various experiments, a Nanoemulsion with 25% olive oil was selected as optimized formulation owing to its much smaller droplet size (143.1 nm), lower polydispersity index, higher zeta potential (-33.3 mV). No considerable changes in droplet size, viscosity and pH occurred during a 30-day storage period at 4 °C. This procedure also suggested that our selected nanoemulsion was physically stable. Additionally, TEM revealed that particles were morphologically spherical. In conclusion, our analyses of the experiments proved the fact that nanoemulsions are promising novel formulations for protein drugs and can greatly enhance stability of protein drugs.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Óleos/química , Proteínas/química , Ondas Ultrassônicas , Água/química , Administração Tópica , Técnicas de Química Sintética , Portadores de Fármacos/síntese química , Emulsões , Tamanho da Partícula , Proteínas/administração & dosagem , Proteínas/uso terapêutico
10.
J Mater Chem B ; 7(16): 2678-2687, 2019 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-31073405

RESUMO

A drug delivery system (DDS) for combined therapy, based on a short oxidized multiwalled carbon nanotube, is reported. It was prepared exploiting a synthetic approach which allowed loading of two drugs, doxorubicin and metformin, the targeting agent biotin and a radiolabeling tag, to enable labeling with Ga-68 or Cu-64 in order to perform an extensive biodistribution study by PET/CT. The DDS biodistribution profile changes with different administration methods. Once administered at therapeutic doses, the DDS showed a marginal beneficial effect on 4T1 tumor bearing mice, a syngeneic and orthotopic model of triple negative breast cancer, with survival extended by 1 week and 2 days in 20% of the mice. This is encouraging given the aggressiveness of the 4T1 tumor. Furthermore our DDS was well tolerated, ruling out concerns regarding the toxicity of carbon nanotubes.


Assuntos
Doxorrubicina/química , Portadores de Fármacos/química , Metformina/química , Nanotubos de Carbono/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Radioisótopos de Cobre/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Radioisótopos de Gálio/química , Marcação por Isótopo , Metformina/farmacocinética , Metformina/farmacologia , Camundongos , Projetos Piloto , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Distribuição Tecidual
11.
Carbohydr Polym ; 216: 129-139, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047049

RESUMO

A novel biotin and arginine modified hydroxypropyl-ß-cyclodextrin (biotin-Arg(pbf)-HP-ß-CD) was successfully synthesized. The hydroxyl groups of HP-ß-CD on the primary faces were coupled with carboxyl groups of biotin using arginine as the functional spacer. Using biotin-Arg(pbf)-HP-ß-CD as the carrier, paclitaxel (PTX)-loaded nanoparticles were developed by modified emulsion solvent evaporation method. The optimized PTX-loaded biotin-Arg(pbf)-HP-ß-CD nanoparticles had a mean diameter of 121.9 nm and zeta potential of -57.7 mV. Transmission electron microscopy (TEM) observation revealed that the nanoparticles were spherical in shape. XRD spectra confirmed the successful encapsulation of PTX. Moreover, in vitro and in vivo evaluations were performed to demonstrate the superior antitumor activity of the PTX-loaded nanoparticles. The cellular uptake study demonstrated the biotin receptor-mediated endocytosis of biotin-Arg(pbf)-HP-ß-CD nanoparticles and the increase of cellular uptake by introduction of biotin and arginine. It can be concluded that the biotin-Arg(pbf)-HP-ß-CD nanoparticles are efficient tumor-targeting drug delivery systems for PTX.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , 2-Hidroxipropil-beta-Ciclodextrina/síntese química , 2-Hidroxipropil-beta-Ciclodextrina/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Arginina/análogos & derivados , Arginina/síntese química , Arginina/toxicidade , Biotina/análogos & derivados , Biotina/síntese química , Biotina/toxicidade , Carcinoma/tratamento farmacológico , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Feminino , Humanos , Células MCF-7 , Camundongos , Nanopartículas/toxicidade , Paclitaxel/química , Paclitaxel/farmacologia , Tamanho da Partícula , Neoplasias do Colo do Útero/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Carbohydr Polym ; 216: 247-259, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047064

RESUMO

Hydrogels are hydrophilic cross-linked polymer networks formed via the simple reaction of one or more monomers with the ability to retain a significant extent of water. Owing to an increased demand for environmentally friendly, biodegradable, and biocompatible products, cellulose nanocrystals (CNCs) with high hydrophilicity have emerged as a promising sustainable material for the formation of hydrogels. The cytocompatibility, swellability, and non-toxicity make CNC hydrogels of great interest in biomedical, biosensing, and wastewater treatment applications. There has been a considerable progress in the research of CNC hydrogels, as the number of scientific publications has exponentially increased (>600%) in the last five years. In this paper, recent progress in CNC hydrogels with particular emphasis on design, materials, and fabrication techniques to control hydrogel architecture, and advanced applications are discussed.


Assuntos
Celulose/química , Hidrogéis/química , Nanocompostos/química , Nanopartículas/química , Adsorção , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Humanos , Hidrogéis/síntese química , Metais Pesados/química , Tecidos Suporte/química , Purificação da Água/métodos
13.
Carbohydr Polym ; 216: 332-342, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047074

RESUMO

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


Assuntos
Quitosana/análogos & derivados , Portadores de Fármacos/química , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , Tensoativos/química , Anidridos Acéticos/química , Acetilação , Animais , Quitosana/síntese química , Quitosana/metabolismo , Quitosana/toxicidade , Dietilaminas/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Fluorescência , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Camundongos , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polietilenoglicóis/toxicidade , Células RAW 264.7 , RNA Interferente Pequeno/química , Rodaminas/química , Tensoativos/síntese química , Tensoativos/metabolismo , Tensoativos/toxicidade
14.
Artif Cells Nanomed Biotechnol ; 47(1): 1702-1709, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31062603

RESUMO

The objective of this study was to hydrophobically modify fenugreek gum (FG) and to further evaluate the potential application of the obtained derivative in liver-targeted drug delivery system. Stearic acid (C18) was conjugated with FG (FG-C18) by a simple esterification reaction. The obtained FG-C18 was then characterized on its chemical structure by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The self-assembled nanomicelles (NMs) of FG-C18 in water were prepared by an ultrasonication method. The average diameter and zeta potential of FG-C18 NMs were 196.70 ± 6.12 nm and -31.79 ± 1.58 mV, respectively. FG-C18 NMs appeared as spherical particles under transmission electron microscopy and possessed a critical micellar concentration of 0.042 mg/ml by pyrene fluorescence probe method. A low toxicity of FG-C18 was revealed on both HepG2 and MCF-7 cells at 0.1-100 mg/ml. Haemolysis of FG-C18 was less than 5%. Cellular uptake of coumarin-6 into HepG2 cells was enhanced by treating with C6-loaded FG-C18 NMs compared to free coumarin-6. These results suggest that FG-C18 have a potential application for a liver targeted drug delivery.


Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Interações Hidrofóbicas e Hidrofílicas , Fígado/metabolismo , Gomas Vegetais/química , Gomas Vegetais/síntese química , Trigonella/química , Transporte Biológico , Técnicas de Química Sintética , Cumarínicos/química , Cumarínicos/metabolismo , Portadores de Fármacos/toxicidade , Hemólise/efeitos dos fármacos , Células Hep G2 , Humanos , Células MCF-7 , Gomas Vegetais/toxicidade
15.
AAPS PharmSciTech ; 20(5): 202, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31140015

RESUMO

Florfenicol (FLO) is a broad-spectrum fluorinated antibiotic used for the treatment of bacterial diseases such as bovine respiratory disease (BRD) in cattle. FLO is a poorly soluble drug in aqueous solution, and its encapsulation in various nanovehicles has been reported to be less than 30%. In this context, the use of bovine serum albumin (BSA) as a nanocarrier for FLO is an interesting approach. BSA is a biocompatible, biodegradable, nontoxic, and nonimmunogenic natural protein, allowing the vehiculization of hydrophilic and hydrophobic drugs with a well-tolerated administration. The present work focuses on the fabrication and characterization of florfenicol-loaded BSA (FLO-BSA NPs), incorporation efficiency, and in vitro release pattern. FLO-BSA NPs nanoparticles were successfully obtained by a simple, low-cost and in a few steps method. The physicochemical properties of the obtained nanoparticles such as size (~ 120 nm), polydispersity index (0.04), and zeta potential (approximately - 40 mV) suggest a high colloidal stability and suitable characteristics for drug delivery. The drug loading reveals a high incorporation of florfenicol in the nanoparticles, in which 33.6 molecules of FLO are encapsulated per each molecule of BSA. The in vitro release profile exhibits an initial stage characterized by the burst effect and then a prolonged release of FLO from the albumin matrix, which is compatible with the Higuchi model and which follows a Fickian diffusion. The results together suggest a suitable tool for future investigations in drug delivery field in order to use this nanomaterial in food, pharmaceutical, and veterinary industry.


Assuntos
Antibacterianos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/metabolismo , Soroalbumina Bovina/farmacocinética , Tianfenicol/análogos & derivados , Animais , Antibacterianos/administração & dosagem , Antibacterianos/síntese química , Bovinos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos/tendências , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/síntese química , Tianfenicol/administração & dosagem , Tianfenicol/síntese química , Tianfenicol/farmacocinética
16.
Carbohydr Polym ; 217: 35-45, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31079683

RESUMO

One of the most effective strategies to enhance the bioavailability and the therapeutic effect of hydrophobic drugs is the use of nanocarriers. We have used κ-carrageenan extracted from Kappaphycus alvarezii to produce oligocarrageenan via an enzymatic degradation process. Polycaprolactone (PCL) chains were grafted onto the oligocarrageenans using a protection/deprotection technique yielding polycaprolactone-grafted oligocarrageenan. The resulting amphiphilic copolymers formed spherical nanomicelles with a mean size of 187 ± 21 nm. Hydrophobic drugs such as curcumin were efficiently encapsulated in the micelles and released within 24-72 h in solution. The micelles were non-cytotoxic and facilitated the uptake of curcumin by endothelial EA-hy926 cells. They also increased the anti-inflammatory effect of curcumin in TNF-alpha-induced inflammation experiments. Finally, in vivo experiments supported a lack of toxicity in zebrafish and thus the potential use of polycaprolactone-grafted oligocarrageenan to improve the delivery of hydrophobic compounds to different organs, including liver, lung and brain as shown in mice.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Portadores de Fármacos/química , Micelas , Oligossacarídeos/química , Poliésteres/química , Acetilação , Animais , Anti-Inflamatórios não Esteroides/química , Carragenina/química , Carragenina/isolamento & purificação , Linhagem Celular , Curcumina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Gammaproteobacteria/enzimologia , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hidrólise , Masculino , Camundongos Endogâmicos C57BL , Oligossacarídeos/síntese química , Oligossacarídeos/isolamento & purificação , Oligossacarídeos/toxicidade , Oxazinas/química , Tamanho da Partícula , Poliésteres/síntese química , Poliésteres/toxicidade , Rodófitas/química , Rifampina/química , Peixe-Zebra
17.
Chem Asian J ; 14(11): 1992-1999, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-30941908

RESUMO

Developing hierarchical supramolecular structures is important for better understanding of various biological functions and possibly generating new materials for biomedical applications. Herein, we report the first examples of functional vesicles derived from cationic spherical organic molecules (C1 -C3 ) which were readily synthesized by reacting a C3 -symmetric tris-benzimmidazole derivative (possessing a 1,3,5-ethyl substituted aromatic core) with 1,3,5-substituted tris-bromomethyl benzene derivatives. Vesicle formation by C1 -C3 was probed by high-resolution microscopy (TEM and AFM), dynamic light scattering (DLS) and fluorescence microscopic imaging of calcein-loaded vesicles. One of the vesicles [Vesicle(C3 )] displayed the ability to load the anticancer drug doxorubicin (DOX). The drug was subsequently released from DOX@Vesicle(C3 ) in a stimuli-responsive manner in presence of the well-known vesicle destroyer Triton X-100, as revealed by in vitro cell migration assay carried out on a highly aggressive human breast cancer cell line (MDA-MB-231).


Assuntos
Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Derivados de Benzeno/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Fluoresceínas/química , Humanos , Microscopia de Fluorescência , Água/química
18.
Nat Commun ; 10(1): 1894, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-31019193

RESUMO

Stabilisation of fragile oligonucleotides, typically small interfering RNA (siRNA), is one of the most critical issues for oligonucleotide therapeutics. Many previous studies encapsulated oligonucleotides into ~100-nm nanoparticles. However, such nanoparticles inevitably accumulate in liver and spleen. Further, some intractable cancers, e.g., tumours in pancreas and brain, have inherent barrier characteristics preventing the penetration of such nanoparticles into tumour microenvironments. Herein, we report an alternative approach to cancer-targeted oligonucleotide delivery using a Y-shaped block catiomer (YBC) with precisely regulated chain length. Notably, the number of positive charges in YBC is adjusted to match that of negative charges in each oligonucleotide strand (i.e., 20). The YBC rendezvouses with a single oligonucleotide in the bloodstream to generate a dynamic ion-pair, termed unit polyion complex (uPIC). Owing to both significant longevity in the bloodstream and appreciably small size (~18 nm), the uPIC efficiently delivers oligonucleotides into pancreatic tumour and brain tumour models, exerting significant antitumour activity.


Assuntos
Antineoplásicos/metabolismo , Neoplasias Encefálicas/terapia , Regulação Neoplásica da Expressão Gênica , Nanoestruturas/química , Oligonucleotídeos/genética , Neoplasias Pancreáticas/terapia , RNA Interferente Pequeno/genética , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Carbocianinas/química , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Corantes Fluorescentes/química , Humanos , Injeções Intravenosas , Masculino , Camundongos , Nanoestruturas/administração & dosagem , Oligonucleotídeos/síntese química , Oligonucleotídeos/metabolismo , Oligonucleotídeos/farmacocinética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Polietilenoglicóis/química , Polilisina/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/síntese química , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacocinética , Eletricidade Estática , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Nat Commun ; 10(1): 1926, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31028250

RESUMO

Recently, surface-enhanced Raman scattering nanoprobes have shown tremendous potential in oncological imaging owing to the high sensitivity and specificity of their fingerprint-like spectra. As current Raman scanners rely on a slow, point-by-point spectrum acquisition, there is an unmet need for faster imaging to cover a clinically relevant area in real-time. Herein, we report the rational design and optimization of fluorescence-Raman bimodal nanoparticles (FRNPs) that synergistically combine the specificity of Raman spectroscopy with the versatility and speed of fluorescence imaging. DNA-enabled molecular engineering allows the rational design of FRNPs with a detection limit as low as 5 × 10-15 M. FRNPs selectively accumulate in tumor tissue mouse cancer models and enable real-time fluorescence imaging for tumor detection, resection, and subsequent Raman-based verification of clean margins. Furthermore, FRNPs enable highly efficient image-guided photothermal ablation of tumors, widening the scope of the NPs into the therapeutic realm.


Assuntos
Neoplasias Encefálicas/terapia , DNA/química , Nanopartículas Metálicas/química , Imagem Óptica/métodos , Neoplasias Ovarianas/terapia , Análise Espectral Raman/métodos , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Linhagem Celular Tumoral , DNA/metabolismo , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Feminino , Corantes Fluorescentes/química , Engenharia Genética , Humanos , Terapia a Laser/instrumentação , Terapia a Laser/métodos , Limite de Detecção , Terapia com Luz de Baixa Intensidade/instrumentação , Terapia com Luz de Baixa Intensidade/métodos , Nanopartículas Metálicas/administração & dosagem , Camundongos , Imagem Óptica/instrumentação , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Imagens de Fantasmas , Prata/química , Análise Espectral Raman/instrumentação , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Biomed Pharmacother ; 112: 108736, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970526

RESUMO

INTRODUCTION: The purpose of the experiment was to survey the therapeutic function of resveratrol (RES)-loaded poly(ethylene glycol)-poly(phenylalanine) (PEG-PPhe) on intestinal ischemia/reperfusion injury (II/RI) via the interaction between CSE/H2S and iNOS/NO compared to free RES in diabetic rats. METHODS: Diabetic rats were pretreated with 20 mg/kg of RES or the RES/PEG-PPhe complex and then subjected to 1 h of ischemia and 3 h of reperfusion. Blood and intestines were collected, intestinal pathological injury was estimated, and the contents of body weight, weights of different tissues, blood glucose, serum insulin, HOMA index, serum nitric oxide (NO) and serum sulfureted hydrogen (H2S) were observed. The dry/wet intestine ratios, the activity of superoxide dismutase (SOD); the contents of methane dicarboxylic aldehyde (MDA), glutathione (GSH), H2S, and NO; and the concentrations of inducible nitric oxide synthase (iNOS) and cystathionine-γ-lyase (CSE) were observed in the intestinal tissues. RESULTS: A significant reduction of weights of different tissues, blood glucose, pathological damage, dry/wet ratios, MDA, NO, iNOS expression and a significant increasement of body weight, serum insulin, HOMA index, SOD, GSH, H2S, CSE expression were observed in both treatment groups. However, a greater reduction of weights of different tissues, blood glucose (7.49-13.49 mmol/L for 72 h vs. the control) and pathological damage, iNOS expression, dry/wet ratios (6.14 ± 0.29 vs. 8.51 ± 0.42), MDA (5.01 ± 0.71 nmol vs. 9.98 ± 0.67 nmol), NO (0.52 ± 0.09 µmol vs. 0.99 ± 0.08 µmol in intestinal tissue; 19.29 ± 0.89 µmol vs. 45.23 ± 1.17 µmol in serum) was observed in the RES/PEG-PPhe group relative to the I/R (P < 0.01 for all); a greater increasement of body weight, serum insulin, HOMA index, SOD (39.79±1.78 U vs. 11.84 ± 1.02 U), GSH (31.25 ± 1.19 mg vs. 10.13 ± 0.64 mg), H2S (39.52 ± 1.32 nmol vs. 13.02 ± 1.03 nmol in intestinal tissue; 9.78 ± 0.79 µmol vs. 3.11 ± 0.85 µmol in serum), CSE expression was observed in the RES/PEG-PPhe group relative to the I/R (P < 0.01 for all). In addition, aminoguanidine (AMI, iNOS inhibitor) reduced I/R injury, and dl-propargylglycine (PAG, CSE inhibitor) increased I/R injury. CONCLUSIONS: The interaction between CSE/H2S and the iNOS/NO-mediated resveratrol/poly(ethylene glycol)-poly(phenylalanine) complex alleviates intestinal ischemia/reperfusion injuries in diabetic rats.


Assuntos
Diabetes Mellitus Experimental/complicações , Portadores de Fármacos/química , Intestinos/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Resveratrol/uso terapêutico , Animais , Cistationina gama-Liase/metabolismo , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Sulfeto de Hidrogênio/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Substâncias Protetoras/administração & dosagem , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Resveratrol/administração & dosagem
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