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dc.contributor.author김용희-
dc.date.accessioned2022-07-28T01:18:03Z-
dc.date.available2022-07-28T01:18:03Z-
dc.date.issued2020-10-
dc.identifier.citationDRUG DELIVERY, v. 27, no. 1, page. 1501-1513en_US
dc.identifier.issn1071-7544-
dc.identifier.issn1521-0464-
dc.identifier.urihttps://www.tandfonline.com/doi/full/10.1080/10717544.2020.1837293-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/171850-
dc.description.abstractIn this study, a system for oral delivery of etoposide (ETP) was designed to avoid the problems associated with low and variable bioavailability of a commercially available ETP emulsion comprised of polyethylene glycol, glycerol, and citric acid anhydrous. ETP was complexed with low-molecular-weight methylcellulose (ETP/LMC) and loaded into a water-in-oil-in-water multiple nanoemulsion to formulate an ETP/LMC-nanoemulsion (ELNE). To further enhance the oral bioavailability, an ionic complex formed by anionic lipid 1,2-didecanoyl-sn-glycero-3-phosphate (sodium salt) and cationic Nα-deoxycholyl-l-lysyl-methylester was incorporated into ELNE, yielding ELNE#7. As expected, ELNE#7 showed 4.07- and 2.25-fold increases in artificial membrane and Caco-2/HT29-MTX-E12 permeability (Papp), respectively, resulting in 224% greater oral bioavailability compared with the commercially available ETP emulsion. In contrast, inhibition of clathrin- and caveola-mediated endocytosis, macropinocytosis, and bile acid transporters by chlorpromazine, genistein, amiloride, and actinomycin D in Caco-2/HT-29-MTX-E12 monolayers reduced the Papp by 45.0%, 20.5%, 28.8%, and 31.1%, respectively. These findings suggest that these routes play important roles in enhancing the oral absorption of ELNE#7. In addition, our mechanistic study suggested that P-glycoprotein did not have an inhibitory effect on the permeation of ELNE#7. Notably, ELNE#7 showed significantly enhanced toxicity in LLC and A549 cells compared with ETP-E. These observations support the improved oral absorption of ETP in ELNE#7, suggesting that it is a better alternative than ETP emulsion.en_US
dc.description.sponsorshipThis research was supported by the Basic Research Program through the National Research Foundation of Korea (NRF), funded by the Korean Government Ministry of Science and ICT [MSIT; Grant No. NRF-2020R1F1A1069889].en_US
dc.language.isoenen_US
dc.publisherTAYLOR & FRANCIS LTDen_US
dc.subjectEtoposideen_US
dc.subjectnanoemulsionen_US
dc.subjectpermeabilityen_US
dc.subjectoral bioavailabilityen_US
dc.subjectbile acid transporter-mediated uptakeen_US
dc.subjectoral absorptionen_US
dc.titleEnhanced oral bioavailability of an etoposide multiple nanoemulsion incorporating a deoxycholic acid derivative-lipid complexen_US
dc.typeArticleen_US
dc.relation.no1-
dc.relation.volume27-
dc.identifier.doi10.1080/10717544.2020.1837293-
dc.relation.page1501-1513-
dc.relation.journalDRUG DELIVERY-
dc.contributor.googleauthorJha, Saurav Kumar-
dc.contributor.googleauthorHan, Hee-Soo-
dc.contributor.googleauthorSubedi, Laxman-
dc.contributor.googleauthorPangeni, Rudra-
dc.contributor.googleauthorChung, Jee Young-
dc.contributor.googleauthorKweon, Seho-
dc.contributor.googleauthorChoi, Jeong Uk-
dc.contributor.googleauthorByun, Youngro-
dc.contributor.googleauthorKim, Yong-Hee-
dc.contributor.googleauthorPark, Jin Woo-
dc.relation.code2020047380-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF ENGINEERING[S]-
dc.sector.departmentDEPARTMENT OF BIOENGINEERING-
dc.identifier.pidyongheekim-
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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