title: Novel flavonoid-based biodegradable nanoparticles for effective oral delivery of etoposide by P-glycoprotein modulation: an in vitro, ex vivo and in vivo investigations.
abstract: A receptor level interaction of etoposide with P-glycoprotein (P-gp) and subsequent intestinal efflux has an adverse effect on its oral absorption. The present work is aimed to enhance the bioavailability of etoposide by co-administering it with quercetin (a P-gp inhibitor) in dual-loaded polymeric nanoparticle formulation. Poly-lactic-co-glycolic acid (PLGA) nanoparticles were optimized for various parameters like o/w phase volume ratio, poly-vinyl alcohol concentration, PLGA concentration and sonication time. The cytotoxicity studies (MTT assay) revealed a 9- and 11-fold decrease in the IC 50 values for etoposide-loaded nanoparticles (ENP) and etoposide + quercetin dual-loaded nanoparticles (EQNP) when compared to that of free etoposide, respectively, and the results were further supported by florescent-activated cell sorter studies. The confocal imaging of the intestinal sections treated with ENP and EQNP containing fluorescent probe (rhodamine) showed the superiority of the EQNP to permeate deeper. Furthermore, pharmacokinetic studies on rats revealed that EQNP exhibited a 2.4-fold increase in bioavailability of etoposide than ENP with no quercetin. The developed loaded nanoparticles have the high potential to enhance the bioavailability of the etoposide and sensitize the resistant cells.
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India and.
authors.forename: Sharmeen
authors.initials: S
authors.lastname: Fatma
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India and.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India and.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: b Product Development Cell , National Institute of Immunology , New Delhi , India.
authors.forename: Amulya Kumar
authors.initials: AK
authors.lastname: Panda
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India and.
authors.forename: Lalit Mohan
authors.initials: LM
authors.lastname: Negi
authors.affiliation: b Product Development Cell , National Institute of Immunology , New Delhi , India.
authors.forename: Dinesh Giri
authors.initials: DG
authors.lastname: Goswami
authors.affiliation: a Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India and.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tariq
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D005047:Etoposide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007408:Intestinal Absorption / Q000187:drug effects*; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D018613:Microscopy, Confocal; D053758:Nanoparticles; D036103:Nanotechnology; D010539:Permeability; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011794:Quercetin / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D012235:Rhodamines / Q000378:metabolism; D012995:Solubility; D013010:Sonication; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005456:Fluorescent Dyes; D012235:Rhodamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005047:Etoposide; D011142:Polyvinyl Alcohol; D011794:Quercetin
keywords: Bioavailability; P-glycoprotein; PLGA; etoposide; nanoparticles; quercetin