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

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• 作者：Mohammad Tariq^a ; Md. Aftab Alam^b ; Anu T. Singh^c ; Amulya K. Panda^d ; Sushama Talegaonkar^a ; ^{stalegaonkar@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; ^{stalegaonkar@ac.in" class="auth_mail" title="E-mail the corresponding author} ; ^{jamaiahamdard@ac.in" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Epirubicin hydrochloride (PubChem CID ; 65348) ; 1 - (3 - Dimethylaminopropyl) - 3 - ethylcarbodiimide hydrochloride (PubChem CID ; 2723939) ; Poly(DL - lactic - co - glycolic acid) (PubChem CID ; 23111554) ; 3 - (4 ; 5 - dimeth ylthiazol - 2 - yl) - 2 ; 5 - diphenyl tetrazolium bromide (PubChem CID ; 64965) ; Mannosamine hydrochloride (PubChem CID ; 9964480) ; Coumarin 6 (PubChem CID ; 100334) ; Sodium Azide (PubChem CID ; 33557) ; Chlorpromazine Hydrochloride (PubChemCID ; 6240) ; Polyvinyl alcohol (Pubchem CID
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 March 2016
• 年：2016
• 卷：501
• 期：1-2
• 页码：18-31
• 全文大小：2787 K

文摘

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.