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Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation

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  • معلومة اضافية
    • Publisher Information:
      Dove Press 2020-10-08
    • نبذة مختصرة :
      Yue Wang, Shuhang Wang, Yingju Xu, Ping Wang, Sukai Li, Lu Liu, Mengyan Liu, Xiangqun Jin School of Pharmacy, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Xiangqun Jin Tel +86-138-4409-0377Fax +86-431-8561-9662Email jinxq@jlu.edu.cnIntroduction: Etoposide refers to a derivative of podophyllotoxin, which plays an important role in the treatment of cancer due to its prominent anti-tumor effect. As a BCS IV drug, etoposide exhibits insufficient aqueous solubility and permeability, thereby limiting its oral absorption. To enhance the oral bioavailability of etoposide, this study developed an amorphous nanopowder.Methods: Based on preliminary screening and experimental design, the stabilizer and preparation process of etoposide nanosuspension were explored. Subsequently, using a Box–Behnken design, the effects of independent factors (ultrasonication time, ratio of two phases and stabilizer concentration) on response variables (particle size and polydispersity index) were studied, and then the formulation was optimized. Finally, nanosuspension was further freeze dried with 1% of mannitol resulting in the formation of etoposide amorphous nanopowder.Results: The optimized etoposide nanopowder showed as spherical particles with an average particle size and polydispersity index of 211.7 ± 10.4 nm and 0.125 ± 0.028. X-ray powder diffraction and differential scanning calorimetry confirmed the ETO in the nanopowder was amorphous. Compared with coarse powder and physical mixture, etoposide nanopowder achieved significantly enhanced saturated solubility and dissolution in various pH environments. The Cmax and AUC0–t of etoposide nanopowder after oral administration in rats were respectively 2.21 and 2.13 times higher than the crude etoposide suspension. Additionally, the Tmax value of nanopowder was 0.25 h, compared with 0.5 h of reference group.Discussion: In the present study, the optimized amorphous n
    • الموضوع:
      International Journal of Nanomedicine; Original Research; info:eu-repo/semantics/article
    • Availability:
      Open access content. Open access content
      info:eu-repo/semantics/openAccess
    • Note:
      text/html
      English
    • Other Numbers:
      NZDMP oai:dovepress.com/57847
      https://www.dovepress.com/etoposide-amorphous-nanopowder-for-improved-oral-bioavailability-formu-peer-reviewed-fulltext-article-IJN
      1202434714
    • Contributing Source:
      DOVE MEDL PRESS LTD
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1202434714
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