RESUMEN
The subject of this paper is to develop a highly conductive Graphene nanoplatelets (GNPs)-Chitosan (CS)/Polyvinyl Alcohol (PVA) (GNPs-CP) nanofibers with excellent mechanical properties. An experimental study was designed to produce nanofibers based on CP nanofibers as matrix and GNPs as reinforcement materials. The microstructure and the surface morphology of the electrospun nanofibers along with their electrical and mechanical properties were examined to study the effect of GNPs content. The SEM results showed that the gradual increase in GNPs content led to a porous web like morphology with no bead. There is a decrease in the diameter of nanofibers by increasing the concentration of GNPs to 1 wt% GNPs from 370 ± 40 nm for CP blend to 144 ± 18 nm for 1 wt% GNPs. Transmission electron microscopy results depicted that GNPs were dispersed uniformly confirmed by the absence of characteristic peak of graphite at 2θ = 26.5°. Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy results indicate the occurrence of a few interactions between GNPs and CP matrix. Nitrogen adsorption/desorption measurement demonstrated that increasing GNPs content increased the specific surface area of nanofibers from 238.377 to 386.708 m2/g for 0 and 1 wt% GNPs content. The test results also show that the presence of GNPs considerably enhances tensile strength, elastic modulus and electrical conductivity. Furthermore, the toughness of GNPs-CP nanofibers including 1 wt% GNPs significantly improved (12-fold) compared to the one for CP nanofibers. So, the proposed composite provides a decent functionality for nanofibers as scaffolds in tissue engineering applications.
Asunto(s)
Quitosano , Grafito , Nanofibras , Conductividad Eléctrica , Alcohol PolivinílicoRESUMEN
Myocardial infarction occurs because coronary arteries insufficiency is one of the major causes of mortality worldwide. Recent studies have shown that tissue engineering of myocardial tissue to regenerate infarcted tissue or engineering of the coronary artery may help overcome this problem. In the present research, gelatin and single-walled carbon nanotube were firstly administrated to physico-chemically and biologically modulate polyurethane nanofibers. Electrospinning, as versatile and effective technique for production of functional nanoscale fiber, was applied. Incorporation of both gelatin and SWNTs reduced mean diameter of nanofibrous scaffolds from 210 to 140 nm, which influenced on initial cell behavior. Possible interaction between gelatin and SWNTs with polyurethane chains was evaluated using FTIR and DSC techniques. Regarding the incorporation of both gelatin and SWNTs, it was found that hydrophilicity of nanofibrous scaffolds dramatically improved. Scaffold degradation profile was adjusted by incorporation of gelatin. Biomimetic mechanical properties of composite scaffolds like normal blood vessel were developed and SWNTs improved the Young modulus and ultimate strength of scaffolds up to 16.47 ± 0.5 and 23.73 ± 0.5 MPa, respectively. However, addition of gelatin increased elongation at break due to its softening effect. The incorporation of the SWNTs led to significant enhancement of electrical conductivity of the scaffolds. Biological evaluation using SEM and MTT assay demonstrated that nanofibrous surface was covered by confluent and dense layer of both myocardial myoblast and endothelial cells after 7 days of culture, which is crucial for cardiovascular tissue engineering. Results verified that the fabricated scaffolds could be effective for cardiovascular tissue engineering.
Asunto(s)
Materiales Biocompatibles/química , Enfermedades Cardiovasculares/terapia , Gelatina/química , Nanotubos de Carbono/química , Poliuretanos/química , Andamios del Tejido/química , Implantación de Prótesis Vascular , Enfermedades Cardiovasculares/cirugía , Proliferación Celular , Vasos Coronarios , Módulo de Elasticidad , Conductividad Eléctrica , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Pruebas Mecánicas , Nanofibras/química , Resistencia a la Tracción , Ingeniería de TejidosRESUMEN
Development of a new class of multifunctional ultrasound-responsive smart nanocarriers that combine therapeutic properties with diagnostic imaging has gained great attention in recent years. Here, we describe the results of ultrasonic nanotherapy of breast cancer using novel alginate-stabilized perfluorohexane nanodroplets. Doxorubicin (Dox)-loaded multifunctional nanodroplets (Dox-NDs) were synthesized via nanoemulsion process and evaluated in vitro and in vivo with focus on cytotoxicity, hemolytic activity, biodistribution, biosafety, and antitumor activity. Echogenic property of nanodroplets was confirmed by B-mode ultrasound imaging. Tumor therapy using Dox-NDs combined with sonication (Dox-ND-US) resulted in strong in vivo antitumor activity characterized by tumor regression which could be because of on demand efficient ultrasound-aided drug release from nanodroplets in tumor tissue under the action of ultrasound. Dox concentration in tumor area for Dox-ND-US treated group reached 10.9µg/g after sonication for 4min (28kHz, 0.034W/cm2), which was 5.2-fold higher compared to non-sonicated Dox-NDs group. The cardiotoxicity of Dox-NDs was much lower than that of free Dox and no hemolytic activity was observed for Dox-NDs. Strong therapeutic effect of these multifunctional nanodroplets combined with their ultrasound-contrast property indicated that this drug delivery system has a great potential in smart cancer-therapy.
Asunto(s)
Neoplasias de la Mama , Alginatos , Doxorrubicina , Portadores de Fármacos , Fluorocarburos , Ácido Glucurónico , Ácidos Hexurónicos , Humanos , Nanoestructuras , Distribución Tisular , UltrasonidoRESUMEN
Perfluorocarbon nanoemulsions are a new class of multifunctional stimuli-responsive nanocarriers which combine the properties of passive-targeted drug carriers, ultrasound imaging contrast agents, and ultrasound-responsive drug delivery systems. Doxorubicin-loaded alginate stabilized perflourohexane (PFH) nanodroplets were synthesized via nanoemulsion preparation method and their ultrasound responsivity, imaging, and therapeutic properties were studied. Doxorubicin was loaded into the nanodroplets (39.2nm) with encapsulation efficiency of 92.2%. In vitro release profile of doxorubicin from nanodroplets was an apparently biphasic release process and 12.6% of drug released from nanodroplets after 24h incubation in PBS, pH=7.4. Sonication with 28kHz therapeutic ultrasound for 10min triggered droplet-to-bubble transition in PFH nanodroplets which resulted in the release of 85.95% of doxorubicin from nanodroplets. Microbubbles formed by acoustic vaporization of the nanodroplets underwent inertial cavitation. In the breast cancer mice models, ultrasound-mediated therapy with doxorubicin-loaded PFH nanodroplets showed excellent anti-cancer effects characterized by tumor regression. Complete tumor regression was observed for the group in which doxorubicin-loaded nanodroplets were combined with ultrasound, whereas the tumor growth inhibition of doxorubicin -loaded nanodroplets was 89.6%. These multifunctional nanodroplets, with excellent therapeutic and ultrasound properties, could be promising drug delivery systems for chemotherapeutic application.
Asunto(s)
Alginatos , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina , Portadores de Fármacos , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Alginatos/química , Alginatos/farmacología , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Femenino , Ácido Glucurónico/química , Ácido Glucurónico/farmacología , Ácidos Hexurónicos/química , Ácidos Hexurónicos/farmacología , Humanos , Ratones , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In the present study the effect of process (homogenization speed) and formulation (polymer-alginate-concentration, surfactant concentration, drug amount, perfluorohexane volume fraction and co-surfactant inclusion) variables on particle size, entrapment efficiency, and drug release kinetics of doxorubicin-loaded alginate stabilized perfluorohexane nanodroplets were evaluated. Particle size and doxorubicin entrapment efficiency were highly affected by formulation and process variables. Increase in homogenization speed resulted in significant decrease in particle size and increase in entrapment efficiency. Polymer concentration and perfluorohexane amount both had similar effect on particle size. Particle size increased by an increase in the amount of both. Entrapment efficiency increased by increasing polymer concentration. In case of surfactant concentration and drug amount, particle size and entrapment efficiency had optimum values and an increase in concentration of both of them behind a certain limit resulted in increase in particle size and decrease in doxorubicin entrapment. In vitro release profile of doxorubicin was an apparently biphasic release process and 7%-13% of drug released after 24h incubation in PBS, pH=7.4, depending on the nanodroplets composition but ultrasound exposure for 10min resulted in triggered release of 85.95% of doxorubicin from optimal formulation (formulation E1 with 39.2nm diameter size and 92.2% entrapment efficiency).