Preparation and in vitro/in vivo evaluation of arsenic trioxide-loaded pH-responsive mesoporous silica nanoparticles / 中草药

ABSTRACT

Objective: To prepare polyacrylic acid grafted arsenic trioxide-loaded pH-responsive mesoporous silica nanoparticles (PAA-ATO-MSNs) and to investigate their physicochemical properties, in vitro release behavior, and pharmacokinetics in rats. Methods: PAA was covalently attached to the exterior surface of amino group functionalized MSNs prepared by co-condensation method and ATO was loaded into them by electrostatic adsorption. Transmission electron microscope (TEM), small angle X-ray diffraction (SAXRD), nitrogen adsorption, thermogravimetric analysis (TGA), fourier transform infrared (FT-IR) spectra, and laser particle size analyzer were used to determine the physicochemical properties. The entrapment efficiency (EE) and drug loading (DL) of PAA-ATO-MSNs were investigated with the method of high speed centrifugation combined with inductively coupled plasma emission spectrum (ICP). The drug release behavior of PAA-ATO-MSNs was studied using dynamic dialysis method, PBS (pH 5.0, 6.0, and 7.4) chosen as release media. Pharmacokinetic behavior of PAA-ATO-MSNs after iv injection in rats was studied. Results: Morphology of PAA-ATO-MSNs was spherical and the mean particle size, Zeta potential, EE, and DL of PAA-ATO-MSNs were (158.60 ± 1.32) nm, (-28.40 ± 0.34) mV, (40.95 ± 3.21)%, and (11.42 ± 1.75)%, respectively. In vitro release behavior of PAA-ATO-MSNs showed pH-responsive characteristic and the cumulative release amount was increased with the decrease of pH value. Compared with ATO-Sol and ATO-MSNs group, t1/2β was significantly prolonged and AUC was significantly increased (P < 0.01). Conclusion: Release of ATO from PAA-ATO-MSNs showed the obvious pH-responsive characteristic and sustained-release in vitro and PAA-ATO-MSNs could improve the pharmacokinetic behavior in rats. PAA-MSNs might be promising carrier to load ATO for cancer therapy.