Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation
Despite the extensive application of methotrexate (MTX) as a chemotherapeutic agent and an immune system suppressor, its therapeutic implementation has been limited due to its poor pharmacokinetics, saturable cellular transport, and insufficient response in some conditions. These limitations have re...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Shiraz University of Medical Sciences
2020-09-01
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| Series: | Trends in Pharmaceutical Sciences |
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| Online Access: | https://tips.sums.ac.ir/article_46833_5a48e389ff2e35d1ca9d30dd7e4b48bf.pdf |
| _version_ | 1819089298655281152 |
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| author | Mahsa Taheri Samirasadat Abolmaali Mozhgan Abedanzadeh Samaneh Mohammadi Sanaz Javanmardi Alimohammad Tamaddon |
| author_facet | Mahsa Taheri Samirasadat Abolmaali Mozhgan Abedanzadeh Samaneh Mohammadi Sanaz Javanmardi Alimohammad Tamaddon |
| author_sort | Mahsa Taheri |
| collection | DOAJ |
| description | Despite the extensive application of methotrexate (MTX) as a chemotherapeutic agent and an immune system suppressor, its therapeutic implementation has been limited due to its poor pharmacokinetics, saturable cellular transport, and insufficient response in some conditions. These limitations have resulted in the development of novel formulations. A pH-dependent MTX release was indicated in our previous study on polyethyleneimine nano-hydrogels; however, it exhibited a fast drug release in phosphate-buffered saline simulating physiologic pH and tonicity conditions. Thus, the current study was aimed at the synthesis of Zn(MTX)2Cl2 complex (MTX-Zn) to modulate drug loading and release under physiologic condition (pH=7.4). MTX-Zn was synthesized by the hydrothermal method and characterized by TLC, FT-IR spectroscopy, and Eriochrome Black T complexometric titration. MTX-Zn was then loaded into the nano-hydrogels and purified through ultrafiltration. The final product was evaluated by DLS, Zeta-potential, and TEM. The variations in the drug loading and release in acidic (tumor) and physiologic media were assessed through UV-Vis spectrophotometry and dialysis methods, respectively. A 5-fold enhancement was observed in the MTX solubility in the acetate buffer; while the Log D value increased from -0.66 to 0.1 upon Zn2+ complexation, reflecting an augmentation in the drug lipophilicity. The MTX-Zn loaded nano-hydrogels exhibited desirable physicochemical features like a small hydrodynamic diameter of 125.7 nm and low polydispersity (PDI = 0.14). The results indicated that, the release tests indicated that the release of MTX-Zn involves a combination of diffusion and swelling mechanisms. MTX-Zn complexation can be applied in the sustained drug release from the nano-hydrogel formulations. |
| first_indexed | 2024-12-21T22:05:43Z |
| format | Article |
| id | doaj.art-0de110354bfd4311b8925df62af9bff9 |
| institution | Directory Open Access Journal |
| issn | 2423-5652 |
| language | English |
| last_indexed | 2024-12-21T22:05:43Z |
| publishDate | 2020-09-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | Trends in Pharmaceutical Sciences |
| spelling | doaj.art-0de110354bfd4311b8925df62af9bff92022-12-21T18:48:42ZengShiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-56522020-09-016314315210.30476/tips.2020.87156.105646833Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal ComplexationMahsa Taheri0Samirasadat AbolmaaliMozhgan Abedanzadeh1Samaneh Mohammadi2Sanaz Javanmardi3Alimohammad Tamaddon4Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, IranCenter for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, IranCenter for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, IranCenter for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, IranCenter for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71345, IranDespite the extensive application of methotrexate (MTX) as a chemotherapeutic agent and an immune system suppressor, its therapeutic implementation has been limited due to its poor pharmacokinetics, saturable cellular transport, and insufficient response in some conditions. These limitations have resulted in the development of novel formulations. A pH-dependent MTX release was indicated in our previous study on polyethyleneimine nano-hydrogels; however, it exhibited a fast drug release in phosphate-buffered saline simulating physiologic pH and tonicity conditions. Thus, the current study was aimed at the synthesis of Zn(MTX)2Cl2 complex (MTX-Zn) to modulate drug loading and release under physiologic condition (pH=7.4). MTX-Zn was synthesized by the hydrothermal method and characterized by TLC, FT-IR spectroscopy, and Eriochrome Black T complexometric titration. MTX-Zn was then loaded into the nano-hydrogels and purified through ultrafiltration. The final product was evaluated by DLS, Zeta-potential, and TEM. The variations in the drug loading and release in acidic (tumor) and physiologic media were assessed through UV-Vis spectrophotometry and dialysis methods, respectively. A 5-fold enhancement was observed in the MTX solubility in the acetate buffer; while the Log D value increased from -0.66 to 0.1 upon Zn2+ complexation, reflecting an augmentation in the drug lipophilicity. The MTX-Zn loaded nano-hydrogels exhibited desirable physicochemical features like a small hydrodynamic diameter of 125.7 nm and low polydispersity (PDI = 0.14). The results indicated that, the release tests indicated that the release of MTX-Zn involves a combination of diffusion and swelling mechanisms. MTX-Zn complexation can be applied in the sustained drug release from the nano-hydrogel formulations.https://tips.sums.ac.ir/article_46833_5a48e389ff2e35d1ca9d30dd7e4b48bf.pdfmethotrexatetransition metal complexnano-hydrogelpoly ethyleneiminerelease |
| spellingShingle | Mahsa Taheri Samirasadat Abolmaali Mozhgan Abedanzadeh Samaneh Mohammadi Sanaz Javanmardi Alimohammad Tamaddon Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation Trends in Pharmaceutical Sciences methotrexate transition metal complex nano-hydrogel poly ethyleneimine release |
| title | Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation |
| title_full | Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation |
| title_fullStr | Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation |
| title_full_unstemmed | Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation |
| title_short | Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation |
| title_sort | modulation of methotrexate release from nano hydrogels via drug transition metal complexation |
| topic | methotrexate transition metal complex nano-hydrogel poly ethyleneimine release |
| url | https://tips.sums.ac.ir/article_46833_5a48e389ff2e35d1ca9d30dd7e4b48bf.pdf |
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