An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres
Our purpose was to test whether a preparation of injectable formulations of dexamethasone (Dex)-loaded microspheres (Dex-Ms) mixed with click-crosslinked hyaluronic acid (Cx-HA) (or Pluronic (PH) for comparison) prolongs therapeutic levels of released Dex. Dex-Ms were prepared using a monoaxial-nozz...
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MDPI AG
2019-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/9/438 |
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| author | Ji Yeon Heo Jung Hyun Noh Seung Hun Park Yun Bae Ji Hyeon Jin Ju Da Yeon Kim Bong Lee Moon Suk Kim |
| author_facet | Ji Yeon Heo Jung Hyun Noh Seung Hun Park Yun Bae Ji Hyeon Jin Ju Da Yeon Kim Bong Lee Moon Suk Kim |
| author_sort | Ji Yeon Heo |
| collection | DOAJ |
| description | Our purpose was to test whether a preparation of injectable formulations of dexamethasone (Dex)-loaded microspheres (Dex-Ms) mixed with click-crosslinked hyaluronic acid (Cx-HA) (or Pluronic (PH) for comparison) prolongs therapeutic levels of released Dex. Dex-Ms were prepared using a monoaxial-nozzle ultrasonic atomizer with an 85% yield of the Dex-Ms preparation, encapsulation efficiency of 80%, and average particle size of 57 μm. Cx-HA was prepared via a click reaction between transcyclooctene (TCO)-modified HA (TCO-HA) and tetrazine (TET)-modified HA (TET-HA). The injectable formulations (Dex-Ms/PH and Dex-Ms/Cx-HA) were fabricated as suspensions and became a Dex-Ms-loaded hydrogel drug depot after injection into the subcutaneous tissue of Sprague Dawley rats. Dex-Ms alone also formed a drug depot after injection. The Cx-HA hydrogel persisted in vivo for 28 days, but the PH hydrogel disappeared within six days, as evidenced by in vivo near-infrared fluorescence imaging. The in vitro and in vivo cumulative release of Dex by Dex-Ms/Cx-HA was much slower in the early days, followed by sustained release for 28 days, compared with Dex-Ms alone and Dex-Ms/PH. The reason was that the Cx-HA hydrogel acted as an external gel matrix for Dex-Ms, resulting in the retarded release of Dex from Dex-Ms. Therefore, we achieved significantly extended duration of a Dex release from an in vivo Dex-Ms-loaded hydrogel drug depot formed by Dex-Ms wrapped in an injectable click-crosslinked HA hydrogel in a minimally invasive manner. In conclusion, the Dex-Ms/Cx-HA drug depot described in this work showed excellent performance on extended in vivo delivery of Dex. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T18:41:53Z |
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| series | Pharmaceutics |
| spelling | doaj.art-412ba49ec7b84ac096b75c99c16a94892022-12-22T04:08:58ZengMDPI AGPharmaceutics1999-49232019-09-0111943810.3390/pharmaceutics11090438pharmaceutics11090438An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded MicrospheresJi Yeon Heo0Jung Hyun Noh1Seung Hun Park2Yun Bae Ji3Hyeon Jin Ju4Da Yeon Kim5Bong Lee6Moon Suk Kim7Department of Molecular Science and Technology, Ajou University, Suwon 16499, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, KoreaDepartment of Polymer Engineering, Pukyong National University, Busan 48547, KoreaDepartment of Molecular Science and Technology, Ajou University, Suwon 16499, KoreaOur purpose was to test whether a preparation of injectable formulations of dexamethasone (Dex)-loaded microspheres (Dex-Ms) mixed with click-crosslinked hyaluronic acid (Cx-HA) (or Pluronic (PH) for comparison) prolongs therapeutic levels of released Dex. Dex-Ms were prepared using a monoaxial-nozzle ultrasonic atomizer with an 85% yield of the Dex-Ms preparation, encapsulation efficiency of 80%, and average particle size of 57 μm. Cx-HA was prepared via a click reaction between transcyclooctene (TCO)-modified HA (TCO-HA) and tetrazine (TET)-modified HA (TET-HA). The injectable formulations (Dex-Ms/PH and Dex-Ms/Cx-HA) were fabricated as suspensions and became a Dex-Ms-loaded hydrogel drug depot after injection into the subcutaneous tissue of Sprague Dawley rats. Dex-Ms alone also formed a drug depot after injection. The Cx-HA hydrogel persisted in vivo for 28 days, but the PH hydrogel disappeared within six days, as evidenced by in vivo near-infrared fluorescence imaging. The in vitro and in vivo cumulative release of Dex by Dex-Ms/Cx-HA was much slower in the early days, followed by sustained release for 28 days, compared with Dex-Ms alone and Dex-Ms/PH. The reason was that the Cx-HA hydrogel acted as an external gel matrix for Dex-Ms, resulting in the retarded release of Dex from Dex-Ms. Therefore, we achieved significantly extended duration of a Dex release from an in vivo Dex-Ms-loaded hydrogel drug depot formed by Dex-Ms wrapped in an injectable click-crosslinked HA hydrogel in a minimally invasive manner. In conclusion, the Dex-Ms/Cx-HA drug depot described in this work showed excellent performance on extended in vivo delivery of Dex.https://www.mdpi.com/1999-4923/11/9/438injectable hydrogeldepotclick-reactionmicrosphereretardation |
| spellingShingle | Ji Yeon Heo Jung Hyun Noh Seung Hun Park Yun Bae Ji Hyeon Jin Ju Da Yeon Kim Bong Lee Moon Suk Kim An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres Pharmaceutics injectable hydrogel depot click-reaction microsphere retardation |
| title | An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres |
| title_full | An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres |
| title_fullStr | An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres |
| title_full_unstemmed | An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres |
| title_short | An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres |
| title_sort | injectable click crosslinked hydrogel that prolongs dexamethasone release from dexamethasone loaded microspheres |
| topic | injectable hydrogel depot click-reaction microsphere retardation |
| url | https://www.mdpi.com/1999-4923/11/9/438 |
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