Enhanced bioavailability of apigenin via preparation of a carbon nanopowder solid dispersion

Abstract

In this study, a novel carbon nanopowder (CNP) drug carrier was developed to improve the oral bioavailability of apigenin (AP). Solid dispersions (SDs) of AP with CNP were prepared, and their in vitro drug release and in vivo performance were evaluated. The physicochemical properties of the formulations were examined by differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. Drug release profiles showed that AP dissolution from the CNP-AP system (weight ratio, 6:1) after 60 minutes improved by 275% compared with that of pure AP. Moreover, the pharmacokinetic analysis of SD formulations in rats showed that the AP area under the curve0-t value was 1.83 times higher for the CNP-AP system than for pure AP, indicating that its bioavailability was significantly improved. In addition, compared with pure AP, SDs had a significantly higher peak and shorter time to peak. Preliminary intestinal toxicity tests indicated that there was no significant difference in the tissues of the rats treated with the CNP-AP system, rats treated with the CNP alone, and controls. In conclusion, CNP-based SDs could be used for enhancing the bioavailability of poorly water-soluble drugs while also improving drug safety.

Keywords: apigenin; carbon nanopowder; dissolution; oral bioavailability; solid dispersions.

Figure 1

The dissolution profiles of AP and SDs at different AP/CNP ratios of 1:2, 1:4, 1:6, and 1:8. Notes: Each point represents the mean ± standard deviation (n=3). ^#P<0.01 versus pure AP at 10 minutes; *P<0.01 versus pure AP at 20 minutes; ^$P<0.01 versus pure AP at 40 minutes; ^&P<0.01 versus pure AP at 60 minutes; ^¥P<0.01 versus pure AP at 80 minutes; ^ΦP<0.01 versus pure AP at 120 minutes; ^ΩP<0.01 versus pure AP at 180 minutes. Abbreviations: AP, apigenin; SD, solid dispersion; CNP, carbon nanopowder.

Figure 2

DSC curves of AP (A), CNP (B), SD at AP/CNP ratio of 1:6 (C) and AP/CNP 1:6 PM (D). Abbreviations: Exo, exothermic direction; DSC, differential scanning calorimetry; AP, apigenin; SD, solid dispersion; CNP, carbon nanopowder; PM, physical mixture.

Figure 3

SEM of AP (A) and AP solid dispersion prepared with an AP/CNP ratio of 1:6 (B); magnification, 8,000×. Abbreviations: SEM, scanning electron microscopy; AP, apigenin; CNP, carbon nanopowder; SEI, secondary electrons image.

Figure 4

X-ray diffraction. Notes: (A) AP, (B) CNP, (C) AP/CNP ratio of 1:6 (w/w) SD, and (D) AP/CNP ratio of 1:6 (w/w) PM. Abbreviations: AP, apigenin; CNP, carbon nanopowder; PM, physical mixture; SD, solid dispersion; w/w, weight/weight.

Figure 5

Mean plasma concentration–time curve of AP in rats after oral administration of AP, SD (AP/CNP ratio of 1:6), and PM (AP/CNP ratio of 1:6) equivalent to 60 mg kg⁻¹ of AP (n=6), respectively. Notes: Values are mean ± SD (n=6/group/time point). **P<0.01 versus pure AP at 0.33 hours; ^##P<0.01 versus pure AP at 0.67 hours; ^$$P<0.01 versus pure AP at 1 hour; ^&&P<0.01 versus pure AP at 1.5 hours; ^¥¥P<0.01 versus pure AP at 2 hours; ^€€P<0.01 versus pure AP at 2.5 hours; ^ΔΔP<0.01 versus pure AP at 3 hours; **P<0.01 versus pure AP at 4 hours; ^ΦP<0.05 versus pure AP at 6 hours; ^ΩP<0.05 versus pure AP at 12 hours. Abbreviations: AP, apigenin; CNP, carbon nanopowder; SD, solid dispersion; PM, physical mixture.

Figure 6

Influences of CNP, SD (AP/CNP ratio of 1:6), and PM (AP/CNP ratio of 1:6) pretreatment on mucosal structures of rats. Notes: (A) control group, (B) CNP group, (C) SD group, and (D) PM group. Magnification, 100×. Abbreviations: CNP, carbon nanopowder; AP, apigenin; SD, solid dispersion; PM, physical mixture.