Mietzner, Raphael and Kade, Christian and Froemel, Franziska and Pauly, Diana and Stamer, W. Daniel and Ohlmann, Andreas and Wegener, Joachim and Fuchshofer, Rudolf and Breunig, Miriam (2020) Fasudil Loaded PLGA Microspheres as Potential Intravitreal Depot Formulation for Glaucoma Therapy. PHARMACEUTICS, 12 (8): 706. ISSN , 1999-4923
Full text not available from this repository. (Request a copy)Abstract
Rho-associated protein kinase (ROCK) inhibitors allow for causative glaucoma therapy. Unfortunately, topically applied ROCK inhibitors suffer from high incidence of hyperemia and low intraocular bioavailability. Therefore, we propose the use of poly (lactide-co-glycolide) (PLGA) microspheres as a depot formulation for intravitreal injection to supply outflow tissues with the ROCK inhibitor fasudil over a prolonged time. Fasudil-loaded microspheres were prepared by double emulsion solvent evaporation technique. The chemical integrity of released fasudil was confirmed by mass spectrometry. The biological activity was measured in cell-based assays using trabecular meshwork cells (TM cells), Schlemm's canal cells (SC cells), fibroblasts and adult retinal pigment epithelium cells (ARPE-19). Cellular response to fasudil after its diffusion through vitreous humor was investigated by electric cell-substrate impedance sensing. Microspheres ranged in size from 3 to 67 mu m. The release of fasudil from microspheres was controllable and sustained for up to 45 days. Released fasudil reduced actin stress fibers in TM cells, SC cells and fibroblasts. Decreased collagen gel contraction provoked by fasudil was detected in TM cells (similar to 2.4-fold), SC cells (similar to 1.4-fold) and fibroblasts (similar to 1.3-fold). In addition, fasudil readily diffused through vitreous humor reaching its target compartment and eliciting effects on TM cells. No negative effects on ARPE-19 cells were observed. Since fasudil readily diffuses through the vitreous humor, we suggest that an intravitreal drug depot of ROCK inhibitors could significantly improve current glaucoma therapy particularly for patients with comorbid retinal diseases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE INHIBITOR; DRUG-DELIVERY; INTRAOCULAR-PRESSURE; AQUEOUS-HUMOR; PARTICLE-SIZE; RELEASE; CELLS; Y-27632; MODEL; DEXAMETHASONE; drug delivery; glaucoma; ROCK inhibitor; fasudil; PLGA microspheres; intravitreal injection; trabecular meshwork; Schlemm's canal; retinal pigment epithelium; Electric Cell-Substrate Impedance Sensing |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Mar 2021 13:54 |
| Last Modified: | 17 Mar 2021 13:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44088 |
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