Background: Ginkgolides are widely used in cardio-protective therapy; however, poor
bioavailability currently limits their application.
Objective: The purpose of this study was to demonstrate whether solid dispersions prepared with LowMolecular-Weight Chitosan (LMWC) could improve the protective effect of ginkgolides on Myocardial
Methods: Ginkgolide Solid Dispersions (GKSD) were prepared with LMWC. Their properties were
then characterized using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. In vivo pharmacokinetic studies were performed in
rats, and the protective effect of GKSD on MI was investigated by western blotting and immunohistochemical analyses.
Results: Drug dissolution testing showed that GDSD were released at a significantly higher rate than
ginkgolides, dissolved by alternative methods, suggesting that LMWC facilitates the release of ginkgolides. Differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and Fourier
transform infrared spectroscopy all showed that GKSD was amorphous. In-vivo testing revealed larger
AUC0-t, higher Cmax, and shorter Tmax for GKSD compared to that in original ginkgolides. Myocardial
injury was induced in rats with isoproterenol to test the protective effect of GKSD. GKSD alleviated MI
and reduced myocardial fibrosis, as observed by Hematoxylin and Eosin staining. Compared with the
crude drug group, the secretion of malonyl dialdehyde and nitric oxide and expression of NOX-2 and
NOX-4 were lower. The activities of the cardiac marker enzymes SOD, CAT, GPX, GPX-1, and GSH
were higher in GKSD-administered rats, indicating a beneficial effect of GKSD in eliminating free radicals during myocardial injury. Additionally, western blotting and immunohistochemical analysis
showed that GKSD markedly reduced the expression of signaling proteins RHOA, ROCK1, ROCK2,
Conclusion: Solid dispersions prepared with low molecular weight chitosan improved the oral bioavailability of ginkgolide and enhanced its protective effect on myocardial injury.