Preparation and Evaluation of Diosgenin Nanocrystals to Improve Oral Bioavailability
- 408 Downloads
Diosgenin (DSG), a well-known steroid sapogenin derived from Dioscorea nipponica Makino and Dioscorea zingiberensis Wright, has a variety of bioactivities. However, it shows low oral bioavailability due to poor aqueous solubility and strong hydrophobicity. The present study aimed to develop DSG nanocrystals to increase the dissolution and then improve the oral bioavailability and biopharmaceutical properties of DSG. DSG nanocrystals were prepared by the media milling method using a combination of pluronic F127 and sodium dodecyl sulfate as surface stabilizers. The physicochemical properties of the optimal DSG nanocrystals were characterized using their particle size distribution, morphology, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy data, and solubility and dissolution test results. Pharmacokinetic studies of the DSG coarse suspension and its nanocrystals were performed in rats. The particle size and polydispersity index of DSG nanocrystals were 229.0 ± 3.7 nm and 0.163 ± 0.064, respectively. DSG retained its original crystalline state during the manufacturing process, and its chemical structure was not compromised by the nanonizing process. The dissolution rate of the freeze-dried DSG nanocrystals was significantly improved in comparison with the original DSG. The pharmacokinetic studies showed that the AUC0–72h and C max of DSG nanocrystals increased markedly (p < 0.01) in comparison with the DSG coarse suspension by about 2.55- and 2.01-fold, respectively. The use of optimized nanocrystals is a good and efficient strategy for oral administration of DSG due to the increased dissolution rate and oral bioavailability of DSG nanocrystals.
KEY WORDSbioavailability diosgenin media milling nanocrystals pharmacokinetics
This study received financial support from the Key Discipline Construction Projects of Higher School, Hebei Province Natural Science Foundation of China (no. H2014406036), Science and Technology Research Key Project of Higher School in Hebei Province (no. ZH2012050), and Science and Technology Research Youth Fund Project of Higher School in Hebei Province (no. QN2015127).
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 1.Fang YW, Zhao JJ, He YZ, Li BG, Xu CJ. Study on the structure of two water-insoluble steroidal saponins of Dioscorea. Acta Pharmaceutical Sinica. 1982;17:388–91.Google Scholar
- 2.Li YM, He BJ, Liu ZY, Jin GS. Study on the water-soluble active ingredient of Dioscorea. J Chin Med Univ. 1979;8:14–6.Google Scholar
- 3.Chen PS, Shih YW, Huang HC, Cheng HW. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression. PLoS One. 2011;6:1–10.Google Scholar
- 12.Ma HY, Zhao ZT, Wang LJ, Wang Y, Zhou QL, Wang BX. Comparative study on anti-hypercholesterolemia activity of diosgenin and total saponin of Discorea panthaica. Chin J Chinese Mater Med. 2002;27:528–31.Google Scholar
- 16.Müller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Adv Drug Deliv Rev. 2001;47:3–19.Google Scholar