Enhanced antitumor efficacy of bile acid-lipid complex-anchored docetaxel nanoemulsion via oral metronomic scheduling
DC Field | Value | Language |
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dc.contributor.author | Jha, Saurav Kumar | - |
dc.contributor.author | Chung, Jee Young | - |
dc.contributor.author | Pangeni, Rudra | - |
dc.contributor.author | Choi, Hyeong Seok | - |
dc.contributor.author | Subedi, Laxman | - |
dc.contributor.author | Kweon, Seho | - |
dc.contributor.author | Choi, Jeong Uk | - |
dc.contributor.author | Byun, Youngro | - |
dc.contributor.author | Kim, Yong-Hee | - |
dc.contributor.author | Park, Jin Woo | - |
dc.date.accessioned | 2021-07-30T04:51:54Z | - |
dc.date.available | 2021-07-30T04:51:54Z | - |
dc.date.created | 2021-05-11 | - |
dc.date.issued | 2020-12 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/1693 | - |
dc.description.abstract | In this study, a system for oral delivery of docetaxel (DTX) was prepared to enhance the oral absorption and anticancer efficacy of DTX via metronomic chemotherapy. DTX was complexed with low-molecular-weight methylcellulose (LMC) and loaded into a nanoemulsion (NE), yielding DTX/LMC-NE (DLNE). To further enhance the oral bioavailability, D-alpha-tocopherol polyethylene glycol succinate and sodium deoxycholate (DOCA) complexed with cationic lipid 1,2-dioleyl-3-trimethylammonium propane (DOTAP) (DOCA-DOTAP [DA-TAP] complex) was incorporated into DLNE, yielding the formulation DLNE#10. As expected, DLNE#10 showed 11.3- and 5.81-fold increases in artificial membrane (P-e) and Caco-2 permeability (P-app), respectively, resulting in 249% greater oral bioavailability, compared to free DTX. In contrast, inhibition of clathrin- and caveolamediated endocytosis, macropinocytosis, and bile acid transporters by chlorpromazine, genistein, amiloride, and actinomycin D in the Caco-2 monolayer reduced the P-app by 55.3%, 44.2%, 35.9%, and 36.5%, respectively; these findings suggest that these routes play important roles in enhancing the oral absorption of DLNE#10. In addition, our mechanistic study suggested that P-glycoprotein (P-gp) did not have an inhibitory effect on the permeation of DLNE#10. Notably, the half-maximal inhibitory concentrations (IC50) of DLNE#10 were 43.5% and 16.8% greater than those of Taxotere (R) in MCF-7 and 4T1 cells, respectively. Finally, the tumor inhibitory rates in 4T1 cell tumor-bearing mice after oral metronomic dosing of DLNE#10 (20 mg/kg DTX) were 5.02- and 1.65-fold greater than the rates in the untreated control group and intravenously injected DTX (10 mg/kg) group, respectively. These observations support the improved oral absorption and enhanced chemotherapeutic efficacy of DTX in DLNE#10 via metronomic chemotherapy, suggesting that it is a better alternative than intravenous Taxotere (R). | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER | - |
dc.title | Enhanced antitumor efficacy of bile acid-lipid complex-anchored docetaxel nanoemulsion via oral metronomic scheduling | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Yong-Hee | - |
dc.identifier.doi | 10.1016/j.jconrel.2020.08.067 | - |
dc.identifier.scopusid | 2-s2.0-85090340135 | - |
dc.identifier.wosid | 000600791600027 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CONTROLLED RELEASE, v.328, pp.368 - 394 | - |
dc.relation.isPartOf | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.title | JOURNAL OF CONTROLLED RELEASE | - |
dc.citation.volume | 328 | - |
dc.citation.startPage | 368 | - |
dc.citation.endPage | 394 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | VITAMIN-E-TPGS | - |
dc.subject.keywordPlus | ION-PAIRING COMPLEX | - |
dc.subject.keywordPlus | P-GLYCOPROTEIN | - |
dc.subject.keywordPlus | INTESTINAL-ABSORPTION | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | ANTICANCER EFFICACY | - |
dc.subject.keywordPlus | TRANSPORT MECHANISM | - |
dc.subject.keywordPlus | DELIVERY SYSTEMS | - |
dc.subject.keywordPlus | DRUG | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordAuthor | Docetaxel | - |
dc.subject.keywordAuthor | Nanoemulsion | - |
dc.subject.keywordAuthor | Bile acid transporter-mediated uptake | - |
dc.subject.keywordAuthor | Oral absorption | - |
dc.subject.keywordAuthor | Metronomic chemotherapy | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0168365920305083?via%3Dihub | - |
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