Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System
A layered double hydroxide (LDH)-based anticancer delivery system was investigated in terms of crystalline phase, particle size, hydrodynamic radius, zeta potential, etc. through in vitro and in vivo study. Size controlled LDH with anticancer drug methotrexate (MTX) incorporation was successfully pr...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/12/1210 |
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| author | Sang-Yong Jung Hyoung-Mi Kim Soonjae Hwang Do-Gak Jeung Ki-Jong Rhee Jae-Min Oh |
| author_facet | Sang-Yong Jung Hyoung-Mi Kim Soonjae Hwang Do-Gak Jeung Ki-Jong Rhee Jae-Min Oh |
| author_sort | Sang-Yong Jung |
| collection | DOAJ |
| description | A layered double hydroxide (LDH)-based anticancer delivery system was investigated in terms of crystalline phase, particle size, hydrodynamic radius, zeta potential, etc. through in vitro and in vivo study. Size controlled LDH with anticancer drug methotrexate (MTX) incorporation was successfully prepared through step-by-step hydrothermal reaction and ion-exchange reaction. The MTX-LDH was determined to have a neutral surface charge and strong agglomeration in the neutral aqueous condition due to the surface adsorbed MTX; however, the existence of proteins in the media dramatically reduced agglomeration, resulting in the hydrodynamic radius of MTX-LDH being similar to the primary particle size. The protein fluorescence quenching assay exhibited that MTX readily reduced the fluorescence of proteins, suggesting that the interaction between MTX and proteins was strong. On the other hand, MTX-LDH showed much less binding constant to proteins compared with MTX, implying that the protein interaction of MTX was effectively blocked by the LDH carrier. The in vivo hemolysis assay after intravenous injection of MTX-LDH showed neither significant reduction in red blood cell number nor membrane damage. Furthermore, the morphology of red blood cells in a mouse model did not change upon MTX-LDH injection. Scanning electron microscopy showed that the MTX-LDH particles were attached on the blood cells without serious denaturation of cellular morphology, taking advantage of the cell hitchhiking property. |
| first_indexed | 2024-03-10T14:06:23Z |
| format | Article |
| id | doaj.art-eb1a0c3409094625970981a662eaf532 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:06:23Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-eb1a0c3409094625970981a662eaf5322023-11-21T00:41:46ZengMDPI AGPharmaceutics1999-49232020-12-011212121010.3390/pharmaceutics12121210Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery SystemSang-Yong Jung0Hyoung-Mi Kim1Soonjae Hwang2Do-Gak Jeung3Ki-Jong Rhee4Jae-Min Oh5Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Jung-gu, KoreaDepartment of Chemistry and Medical Chemistry, Yonsei University MIRAE Campus, College of Science and Technology, Wonju 26493, Gangwon-do, KoreaNatural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung 25451, Gangwon-do, KoreaDepartment of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Jung-gu, KoreaDepartment of Biomedical Laboratory Science, Yonsei University MIRAE Campus, College of Health Sciences, Wonju 26493, Gangwon-do, KoreaDepartment of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Jung-gu, KoreaA layered double hydroxide (LDH)-based anticancer delivery system was investigated in terms of crystalline phase, particle size, hydrodynamic radius, zeta potential, etc. through in vitro and in vivo study. Size controlled LDH with anticancer drug methotrexate (MTX) incorporation was successfully prepared through step-by-step hydrothermal reaction and ion-exchange reaction. The MTX-LDH was determined to have a neutral surface charge and strong agglomeration in the neutral aqueous condition due to the surface adsorbed MTX; however, the existence of proteins in the media dramatically reduced agglomeration, resulting in the hydrodynamic radius of MTX-LDH being similar to the primary particle size. The protein fluorescence quenching assay exhibited that MTX readily reduced the fluorescence of proteins, suggesting that the interaction between MTX and proteins was strong. On the other hand, MTX-LDH showed much less binding constant to proteins compared with MTX, implying that the protein interaction of MTX was effectively blocked by the LDH carrier. The in vivo hemolysis assay after intravenous injection of MTX-LDH showed neither significant reduction in red blood cell number nor membrane damage. Furthermore, the morphology of red blood cells in a mouse model did not change upon MTX-LDH injection. Scanning electron microscopy showed that the MTX-LDH particles were attached on the blood cells without serious denaturation of cellular morphology, taking advantage of the cell hitchhiking property.https://www.mdpi.com/1999-4923/12/12/1210colloidal propertyin vivolayered double hydroxidehemolysisparticle size |
| spellingShingle | Sang-Yong Jung Hyoung-Mi Kim Soonjae Hwang Do-Gak Jeung Ki-Jong Rhee Jae-Min Oh Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System Pharmaceutics colloidal property in vivo layered double hydroxide hemolysis particle size |
| title | Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System |
| title_full | Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System |
| title_fullStr | Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System |
| title_full_unstemmed | Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System |
| title_short | Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System |
| title_sort | physicochemical properties and hematocompatibility of layered double hydroxide based anticancer drug methotrexate delivery system |
| topic | colloidal property in vivo layered double hydroxide hemolysis particle size |
| url | https://www.mdpi.com/1999-4923/12/12/1210 |
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