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Enhanced the Bioavailability of Sterile 20(S)-Protopanaxadiol Nanocrystalline Suspension Coated by Bovine Serum Albumin for Intramuscular Injection: In Vitro and In Vivo Evaluation

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Abstract

The aim of this study was to prepare a 20(S)-protopanaxadiol nanocrystalline suspension and enhance the bioavailability of 20(S)-protopanaxadiol by intramuscular injection. 20(S)-Protopanaxadiol nanocrystalline suspension was prepared using an anti-solvent combined with ultrasonic approach, in which meglumine and bovine serum albumin were screened as the optimized stabilizer and the coating agent during spray drying process, respectively. The optimal nanocrystallines were nearly spherical with a uniform particle size distribution, the mean particle size, polydispersity index, and drug loading of which were 151.20 ± 2.54 nm, 0.11 ± 0.01, and 47.15% (w/w), respectively. Sterile 20(S)-protopanaxadiol nanocrystalline suspension was obtained by passing through a 0.22-μm membrane, and the average filtration efficiency (FE%) was 99.96%. The cumulative release percentage of 20(S)-protopanaxadiol nanocrystalline suspension was 92.36% 20(S)-protopanaxadiol within 60 min in vitro, which was relatively rapid compared with that of the physical mixture for 12.51% and the 20(S)-protopanaxadiol bulk powder for 9.71% during the same time interval. The sterile 20(S)-protopanaxadiol nanocrystalline suspension caused minimal irritation responses by histological examination, indicating a good biocompatibility between the 20(S)-protopanaxadiol nanocrystalline suspension and muscle tissues. In pharmacokinetic study, the absolute bioavailability of 20(S)-protopanaxadiol nanocrystalline suspension for intramuscular injection and for oral gavage was 5.99 and 0.03, respectively. In summary, the 20(S)-protopanaxadiol nanocrystalline via intramuscular injection is an efficient drug delivery system to improve its bioavailability.

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Acknowledgments

We thank Amanda Pearce’s correction for the manuscript.

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Authors and Affiliations

  1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Hui Zhang, Hongbing Liu, Pan Qi, Jingxin Gou, Yu Zhang, Haibing He, Xing Tang & Yue Yuan

  2. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Silin Wang

  3. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Haibin Hu

  4. School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Tian Yin

  5. Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, 222047, People’s Republic of China

    Tian Yin

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  1. Hui Zhang
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Correspondence to Tian Yin or Yue Yuan.

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Zhang, H., Liu, H., Qi, P. et al. Enhanced the Bioavailability of Sterile 20(S)-Protopanaxadiol Nanocrystalline Suspension Coated by Bovine Serum Albumin for Intramuscular Injection: In Vitro and In Vivo Evaluation. AAPS PharmSciTech 20, 305 (2019). https://doi.org/10.1208/s12249-019-1498-5

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