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Article

Fasudil Loaded PLGA Microspheres as Potential Intravitreal Depot Formulation for Glaucoma Therapy

1
Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany
2
Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany
3
Department of Human Anatomy and Embryology, University of Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany
4
Experimental Ophthalmology, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany
5
Department of Ophthalmology, Duke University, Durham, NC 27710, USA
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Department of Ophthalmology, Ludwig-Maximilians-University Munich, Mathildenstrasse 8, 80336 Munich, Germany
7
Fraunhofer Research Institution for Microsystems and Solid State Technologies EMFT, Universitaetsstrasse 31, 93040 Regensburg, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(8), 706; https://doi.org/10.3390/pharmaceutics12080706
Received: 26 June 2020 / Revised: 21 July 2020 / Accepted: 23 July 2020 / Published: 27 July 2020
(This article belongs to the Special Issue Ophthalmic Drug Delivery)
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 µm. 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 (~2.4-fold), SC cells (~1.4-fold) and fibroblasts (~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. View Full-Text
Keywords: drug delivery; glaucoma; ROCK inhibitor; fasudil; PLGA microspheres; intravitreal injection; trabecular meshwork; Schlemm’s canal; retinal pigment epithelium; Electric Cell-Substrate Impedance Sensing drug delivery; glaucoma; ROCK inhibitor; fasudil; PLGA microspheres; intravitreal injection; trabecular meshwork; Schlemm’s canal; retinal pigment epithelium; Electric Cell-Substrate Impedance Sensing
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MDPI and ACS Style

Mietzner, R.; Kade, C.; Froemel, F.; Pauly, D.; Stamer, W.D.; Ohlmann, A.; Wegener, J.; Fuchshofer, R.; Breunig, M. Fasudil Loaded PLGA Microspheres as Potential Intravitreal Depot Formulation for Glaucoma Therapy. Pharmaceutics 2020, 12, 706. https://doi.org/10.3390/pharmaceutics12080706

AMA Style

Mietzner R, Kade C, Froemel F, Pauly D, Stamer WD, Ohlmann A, Wegener J, Fuchshofer R, Breunig M. Fasudil Loaded PLGA Microspheres as Potential Intravitreal Depot Formulation for Glaucoma Therapy. Pharmaceutics. 2020; 12(8):706. https://doi.org/10.3390/pharmaceutics12080706

Chicago/Turabian Style

Mietzner, Raphael, Christian Kade, Franziska Froemel, Diana Pauly, W. D. Stamer, Andreas Ohlmann, Joachim Wegener, Rudolf Fuchshofer, and Miriam Breunig. 2020. "Fasudil Loaded PLGA Microspheres as Potential Intravitreal Depot Formulation for Glaucoma Therapy" Pharmaceutics 12, no. 8: 706. https://doi.org/10.3390/pharmaceutics12080706

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