Abstract
Using (3–glycidoxypropyl) trimethoxysilane (GPTMS) as the cross-linking agent, a novel pH-responsive nanocarrier based on chitosan/mesoporous silica hybrids (MSNs/CS) was successfully fabricated. The optimal technological conditions for the synthesis of MSNs or MSNs/CS were investigated, and the composites were characterized using field emission electron microscopy (FE-SEM), Fourier transform infrared (FT-IR) spectra, X-Ray diffraction (XRD), thermogravimetric analysis (TGA), and nitrogen adsorption/desorption isotherms, among other techniques. Haemolysis and MTT assays showed that MSNs and MSNs/CS had good biocompatibility, when the concentration of MSNs/CS was as high as 2 mg/mL, the hemolysis rate was still lower than 5%, and the cell viability of the carrier material was still greater than 80% when the concentration of MSNs/CS reached 250 μg/mL. Doxorubicin hydrochloride (DOX•HCl), as the model therapeutic agent, was released faster in simulated tumor microenvironment, and the drug loading and encapsulation efficiency of MSNs/CS were 32.47 ± 0.478% and 96.164 ± 0.0643%, respectively. Moreover, the in vitro drug release curve of MSNs/CS is highly fitted to the Higuchi equation, which indicates that the MSNs/CS-DOX•HCl system has pH response and sustained-release characteristics. Intracellular drug uptake and release experiments as well as the in-vitro anti-tumor efficacy, both demonstrated that loading DOX•HCl on the MSNs/CS improved the drug's tumor-targeted therapeutic effect. MSNs/CS synthesized by GPTMS was shown to be a novel idea for the research and development of targeted sustained and controlled-release preparations.
Published Version
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