Fabrication of Stable Apigenin Nanosuspension with PEG 400 as Antisolvent for Enhancing the Solubility and Bioavailability.

The purpose of this paper is to prepare a stable apigenin nanosuspension with a drug concentration of 1.11 mg/mL through green and efficient antisolvent method. Compared with the traditional preparation process that may use toxic reagents, in this study, a green and effective strategy was applied for the preparation of stable apigenin nanosuspension by using an antisolvent method with PEG 400 as antisolvent to improve the solubility and bioavailability. It was found that the particle size of apigenin nanosuspension was about 280 nm, and the solubility and dissolution of the nanosuspension were 33 and 3 times higher than that of the apigenin, respectively. Pharmacokinetic study showed that the Cmax and AUC 0-8 h values of the nanosuspension in fasting rats achieved about 6- and 2.5-fold enhancement than that of the apigenin, respectively. Stability test showed that the apigenin nanosuspension could be stored stably for 12 months at 25℃. Taken together, the antisolvent method with PEG 400 was proven to be a green and effective method to prepare the stable nanosuspension of poorly soluble drugs.

pH-triggered sustained release of arsenic trioxide by polyacrylic acid capped mesoporous silica nanoparticles for solid tumor treatment in vitro and in vivo.

Arsenic trioxide (As2O3, ATO), a FDA approved drug for hematologic malignancies, was proved of efficient growth inhibition of cancer cell in vitro or solid tumor in vivo. However, its effect on solid tumor in vivo was hampered by its poor pharmacokinetics and dose-limited toxicity. In this study, a polyacrylic acid capped pH-triggered mesoporous silica nanoparticles was conducted to improve the pharmacokinetics and enhance the antitumor effect of arsenic trioxide. The mesoporous silica nanoparticles loaded with arsenic trioxide was grafted with polyacrylic acid (PAA-ATO-MSN) as a pH-responsive biomaterial on the surface to achieve the release of drug in acidic microenvironment of tumor, instead of burst release action in circulation. The nanoparticles were characterized with uniform grain size (particle sizes of 158.6 ± 1.3 nm and pore sizes of 3.71 nm, respectively), historically comparable drug loading efficiency (11.42 ± 1.75%), pH-responsive and strengthened sustained release features. The cell toxicity of amino groups modified mesoporous silica nanoparticles (NH2-MSN) was significantly reduced by capping of polyacrylic acid. In pharmacokinetic studies, the half time (t1/2ß) was prolonged by 1.3 times, and the area under curve) was increased by 2.6 times in PAA-ATO-MSN group compared with free arsenic trioxide group. Subsequently, the antitumor efficacy in vitro (SMMC-7721 cell line) and in vivo (H22 xenografts) was remarkably enhanced indicated that PAA-ATO-MSN improved the antitumor effect of the drug. These results suggest that the polyacrylic acid capped mesoporous silica nanoparticles (PAA-MSN) will be a promising nanocarrier for improving pharmacokinetic features and enhancing the anti-tumor efficacy of arsenic trioxide.