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  • Title: Biodegradable polymeric nanoparticles for oral delivery of epirubicin: In vitro, ex vivo, and in vivo investigations.
    Author: Tariq M, Alam MA, Singh AT, Iqbal Z, Panda AK, Talegaonkar S.
    Journal: Colloids Surf B Biointerfaces; 2015 Apr 01; 128():448-456. PubMed ID: 25769281.
    Abstract:
    Epirubicin (EPI) is an anthracycline antineoplastic agent, commercially available for intravenous administration only and its oral ingestion continues to remain a challenge. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for oral bioavailability enhancement of epirubicin. Developed formulation revealed particle size, 235.3±15.12 nm, zeta potential, -27.5±0.7 mV and drug content (39.12±2.13 μg/mg), with spherical shape and smooth surface. Cytotoxicity studies conducted on human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of epirubicin loaded poly-lactic-co-glycolic acid nanoparticles (EPI-NPs) over free epirubicin solution (EPI-S). Further, flow cytometric analysis demonstrated improved drug uptake through EPI-NPs and elucidated the dominance of caveolae mediated endocytosis for nanoparticles uptake. Transport study accomplished on human colon adenocarcinoma cell line (Caco-2) showed 2.76 fold improvement in permeability for EPI-NPs as compared to EPI-S (p<0.001) whereas a 4.49 fold higher transport was observed on rat ileum; a 1.8 fold higher (p<0.01) in comparison to Caco-2 cell lines which confirms the significant role of Peyer's patches in absorption enhancement. Furthermore, in vivo pharmacokinetic studies also revealed 3.9 fold improvement in oral bioavailability of EPI through EPI-NPs. Henceforth, EPI-NPs is a promising approach to replace pre-existing intravenous therapy thus providing "patient care at home".
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