An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres
| Autor: | Yun Bae Ji, Hyeon Jin Ju, Jung Hyun Noh, Ji Yeon Heo, Moon Suk Kim, Da Yeon Kim, Bong Lee, Seung Hun Park |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
endocrine system
Depot Pharmaceutical Science injectable hydrogel lcsh:RS1-441 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Article lcsh:Pharmacy and materia medica chemistry.chemical_compound In vivo depot Hyaluronic acid medicine polycyclic compounds Dexamethasone Chemistry click-reaction Poloxamer 021001 nanoscience & nanotechnology In vitro retardation 0104 chemical sciences medicine.anatomical_structure microsphere Click chemistry 0210 nano-technology hormones hormone substitutes and hormone antagonists medicine.drug Subcutaneous tissue |
| Zdroj: | Pharmaceutics, Vol 11, Iss 9, p 438 (2019) Pharmaceutics Volume 11 Issue 9 |
| ISSN: | 1999-4923 |
| Popis: | 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 &mu m. 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. |
| Databáze: | OpenAIRE |
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