RESUMEN
Temperature and H2O2 dual-responsive nanoparticles were fabricated from ferrocene modified mesoporous silica (MSN-Fc) and ß-cyclodextrin-poly(N-isopropylacrylamide) (ß-CD-PNIPAM) star-shaped polymer due to the host-guest interactions for controlled drug release. The formation and structure of ß-CD-PNIPAM@MSN-Fc composite nanoparticles was confirmed by FTIR, TGA, TEM and N2 adsorption-desorption isotherms. The size of nanoparticles was about 100-150 nm with well-ordered mesoporous structure and PNIPAM chains coating on the surface as outer shell. The channels of MSNs and hydrophobic cavities of ß-CD were all contributed to the high drug loading capacity for nanoparticles. The release of DOX from nanoparticles was enhanced with the increase of temperature above LCST or adding H2O2 in ambient O2. The release kinetics were studied using different models to explain drug release mechanism. Furthermore, the drug loaded composite nanoparticles exhibited excellent anti-cancer activity.
Asunto(s)
Preparaciones de Acción Retardada/farmacología , Liberación de Fármacos , Peróxido de Hidrógeno/química , Nanopartículas/química , Dióxido de Silicio/química , Temperatura , Resinas Acrílicas/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Compuestos Ferrosos/química , Células HeLa , Humanos , Cinética , Metalocenos/química , Porosidad , Espectroscopía Infrarroja por Transformada de Fourier , Termogravimetría , beta-Ciclodextrinas/químicaRESUMEN
In this paper, temperature and pH dual-sensitive supramolecular micelles were constructed from star polymer ß-cyclodextrin-poly(N-isopropylacrylamide) (ß-CD-PNIPAM) and benzimidazole terminated poly(ε-caprolactone) (BM-PCL). The supramolecular micelles were formed based on the reversible host-guest recognition between ß-CD and BM. The size of supramolecular micelles was about 50-100 nm and the LCST was about 30.5 â. The drug loading efficiency of supramolecular micelles for DOX was high due to the hydrophobic micelles core of PCL and hydrophobic cavity of ß-CD. The release of drugs from supramolecular micelles was suppressed at neutral solution and room temperature but accelerated at acidic solution and 37 â. The drug loaded supramolecular micelles exhibited higher anti-cancer activity than free drugs. These temperature and pH dual-sensitive supramolecular micelles might possess potential applications for anticancer drug delivery.
Asunto(s)
Resinas Acrílicas/química , Resinas Acrílicas/síntesis química , Sistemas de Liberación de Medicamentos , Micelas , Temperatura , beta-Ciclodextrinas/química , beta-Ciclodextrinas/síntesis química , Bencimidazoles/química , Muerte Celular/efectos de los fármacos , Doxorrubicina/farmacología , Células HeLa , Humanos , Hidrodinámica , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Poliésteres/química , Espectroscopía de Protones por Resonancia Magnética , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad EstáticaRESUMEN
A well-defined double hydrophilic poly(ß-cyclodextrin)-containing diblock copolymer PEG-b-PCD was synthesized by atom transfer radical polymerization (ATRP). Complex micelles with defined core-shell structure were formed based on the host-guest interactions between poly(ß-cyclodextrin) block copolymer and benzimidazole modified poly(ε-caprolactone) (BM-PCL). The hydrophobic PCD/BM-PCL resided in the core of micelles, while the hydrophilic poly(ethylene glycol) (PEG) chains acted as the micelles shell. The micelles exhibited regular spheres with diameter of about 255nm. The drug loading efficiency of micelles for doxorubicin (DOX) was high due to the hydrophobic core containing poly(ß-CD) and PCL. The in vitro release demonstrated that DOX-loaded polymer micelles exhibited an enhanced sustained manner after an initial burst release. The release of drugs was accelerated as the pH reduced from 7.0 to 2.0 and the temperature increased from 25 to 37°C. These results indicate that the complex micelles have potential applications in controlled drug delivery.
Asunto(s)
Bencimidazoles/química , Micelas , Poliésteres/química , Polímeros/química , Glicoles de Propileno/química , beta-Ciclodextrinas/química , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Polietilenglicoles/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
In this paper, sensitive polymeric hollow spheres self-assembled from chitosan-grafted-ß-cyclodextrin (CS-g-CD) and sodium tripolyphosphate (TPP) were prepared for controlled release of doxorubicin (DOX). The assemblies were formed by electrostatic interactions between positively charged amino group in CS-g-CD and negatively charged phosphate in TPP. The hollow spheres with diameters about 100nm were confirmed by transmission electron microscopy (TEM) and laser particle analyzer. The microspheres with hollow cavity were beneficial to improve the drug loading capacity for DOX with entrapment efficiency above 60%. The cumulative release of DOX from CS-g-CD/TPP hollow microspheres increased with the decrease of pH and the increase of temperature or ionic strength. At 37 °C and pH 5.2, the maximum drug release was above 90% with a continuous release rate. In-vitro cytotoxicity tests indicate that drug loaded hollow spheres exhibited evidently inhibition against cancer cells. These sensitive polymeric hollow spheres are expected to be used in biomedical field as potential carrier.