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Surface decorated nanoparticles as surrogate carriers for improved transport and absorption of epirubicin across the gastrointestinal tract: Pharmacokinetic and pharmacodynamic investigations.

Author information

Affiliations

  • 1. Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
      Authors
    • Tariq M 1
    • Talegaonkar S 1
    (2 authors)
  • 2. Department Pharmacy, Galgotia University, Greater Noida, India.
      Authors
    • Alam MA 2
    (1 author)
  • 3. Dabur Research Foundation, 22, Site IV, Sahibabad, Ghaziabad, Uttar Pradesh, India.
      Authors
    • Singh AT 3
    (1 author)
  • 4. National Institute of Immunology, Aruna Asaf Ali Road, New Delhi, India.
      Authors
    • Panda AK 4
    (1 author)

ORCIDs linked to this article

International Journal of Pharmaceutics, 23 Jan 2016, 501(1-2):18-31
https://doi.org/10.1016/j.ijpharm.2016.01.054 PMID: 26812610 

Abstract 

Epirubicin (EPI) is a P-gp substrate antracycline analogue which elicits poor oral bioavailability. In the present work, EPI loaded poly-lactide-co-glycolic acid nanoparticles (PLGA-NPs) were prepared by double emulsion approach and superficially decorated with polyethylene glycol (EPI-PNPs) and mannosamine (EPI-MNPs). Average hydrodynamic particle size of EPI-PNPs and EPI-MNPs was found 248.63 ± 12.36 and 254.23 ± 15.16 nm, respectively. Cytotoxicity studies were performed against human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of EPI-PNPs and EPI-MNPs over free epirubicin solution (EPI-S). Further, confocal laser scanning microscopy (CLSM) and flow cytometric analysis (FACS) demonstrated enhanced drug uptake through EPI-PNPs and EPI-MNPs and elucidated dominance of caveolae mediated endocytosis for NPs uptake. Cellular transport conducted on human colon adenocarcinoma cell line (Caco-2) showed 2.45 and 3.17 folds higher permeability of EPI through EPI-PNPs and EPI-MNPs when compared with EPI-S (p<0.001) while permeability of EPI was found 5.23 and 5.67 folds higher across rat ileum, respectively. Furthermore, pharmacokinetic studies demonstrated 4.7 and 5.57 folds higher oral bioavailability through EPI-PNPs and EPI-MNPs when compared with EPI-S. In addition, both, EPI-PNPs and EMNPs showed tumor suppression comparable to indicated route (i.v. injection). EPI-MNPs showed 1.18 folds higher bioavailability and better tumor suppression than EPI-PNPs.

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Read article at publisher's site: https://doi.org/10.1016/j.ijpharm.2016.01.054

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Funding 

Funders who supported this work.

Department of Biotechnology (DBT)

    Jamia Hamdard

      Jamia Millia Islamia

        SAIF (AIIMS)