title: Biodegradable polymeric nanoparticles for oral delivery of epirubicin: In vitro, ex vivo, and in vivo investigations.
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".
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tariq
authors.affiliation: Product Development Cell, National Institute of Immunology, New Delhi, India.
authors.forename: Md Aftab
authors.initials: MA
authors.lastname: Alam
authors.affiliation: Dabur Research Foundation, 22, Site IV, Sahibabad, Ghaziabad, Uttar Pradesh, India.
authors.forename: Anu T
authors.initials: AT
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: Product Development Cell, National Institute of Immunology, New Delhi, India.
authors.forename: Amulya K
authors.initials: AK
authors.lastname: Panda
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India. Electronic address: stalegaonkar@gmail.com.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D015251:Epirubicin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010581:Peyer's Patches / Q000187:drug effects / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015251:Epirubicin
keywords: Cellular transport; Cellular uptake; Epirubicin; Intestinal transport; Oral bioavailability; PLGA NPs