Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 최한곤 | - |
dc.date.accessioned | 2023-06-23T02:09:33Z | - |
dc.date.available | 2023-06-23T02:09:33Z | - |
dc.date.issued | 2022-10 | - |
dc.identifier.citation | PHARMACEUTICS, v. 14, NO. 10, article no. 2073, | - |
dc.identifier.issn | 1999-4923;1999-4923 | - |
dc.identifier.uri | https://www.mdpi.com/1999-4923/14/10/2073 | en_US |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/182304 | - |
dc.description.abstract | The poor aqueous solubility and/or permeability and thereby limited bioavailability largely restricts the pharmaco-therapeutic implications of potent anticancer drugs such as methotrexate (MTX). Furthermore, MTX's inherently unstable nature makes it difficult to develop a viable oral formulation. In this study we developed the spray-dried amorphous inclusion complexes of MTX with native beta-cyclodextrin (beta-CD) and its derivatives, namely HP-beta-CD, M-beta-CD, and DM-beta-CD to enhance the aqueous solubility, photostability, permeability, and oral bioavailability of MTX in rats. Our findings show that the 1:1 stoichiometry ratio of MTX and CDs improves the aqueous solubility, stability, and pharmacokinetic profiles of the drug, the better results being obtained particularly with DM-beta-CD as a host, which has a higher complexation ability with the drug compared to other beta-CDs. Specifically, the pharmacokinetic analysis demonstrated 2.20- and 3.29-fold increments in AUC and Cmax, respectively, in comparison to free MTX. Even though the absorptive permeability of MTX and MTX/DM-beta-CD inclusion complexes was similar, the efflux of the absorbed MTX from ICs was significantly lower compared to the free MTX (4.6- vs. 8.0-fold). Furthermore, the physicochemical characterization employing SEM, DSC, and PXRD confirmed the transformation of crystalline MTX to its amorphous state. In solution, H-1 NMR studies revealed that MTX embedded into the DM-beta-CD cavity resulting in both H-3 and H-5 chemical shifts implied the presence of intermolecular interaction between the drug and CD moiety. It was, therefore, evident that an MTX IC could be a successful oral formulation technique, preventing MTX degradation and enhancing its pharmacologically relevant properties. | - |
dc.description.sponsorship | This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (No. 2020R1A5A2017323 and No. 2021R1C1C1010721). | - |
dc.language | en | - |
dc.publisher | MDPI | - |
dc.subject | inclusion complex | - |
dc.subject | methotrexate | - |
dc.subject | solubility | - |
dc.subject | bioavailability | - |
dc.subject | permeability | - |
dc.subject | beta-cyclodextrin (beta-CD) | - |
dc.title | Alternative Methotrexate Oral Formulation: Enhanced Aqueous Solubility, Bioavailability, Photostability, and Permeability | - |
dc.type | Article | - |
dc.relation.no | 10 | - |
dc.relation.volume | 14 | - |
dc.identifier.doi | 10.3390/pharmaceutics14102073 | - |
dc.relation.journal | PHARMACEUTICS | - |
dc.contributor.googleauthor | Giri, Bhupendra Raj | - |
dc.contributor.googleauthor | Yang, Hyun Seok | - |
dc.contributor.googleauthor | Song, Im-Sook | - |
dc.contributor.googleauthor | Choi, Han-Gon | - |
dc.contributor.googleauthor | Cho, Jung Hyun | - |
dc.contributor.googleauthor | Kim, Dong Wuk | - |
dc.sector.campus | E | - |
dc.sector.daehak | 약학대학 | - |
dc.sector.department | 약학과 | - |
dc.identifier.pid | hangon | - |
dc.identifier.article | 2073 | - |
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