Fasudil loaded PLGA microspheres as potential intravitreal depot formulation for glaucoma therapy

Raphael Mietzner, Christian Kade, Franziska Froemel, Diana Pauly, W. Daniel Stamer, Andreas Ohlmann, Joachim Wegener, Rudolf Fuchshofer, Miriam Breunig

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Article number706
Pages (from-to)1-22
Number of pages22
Issue number8
StatePublished - Aug 2020
Externally publishedYes


  • Drug delivery
  • Electric Cell-Substrate Impedance Sensing
  • Fasudil
  • Glaucoma
  • Intravitreal injection
  • PLGA microspheres
  • Retinal pigment epithelium
  • ROCK inhibitor
  • Schlemm’s canal
  • Trabecular meshwork

ASJC Scopus subject areas

  • Pharmaceutical Science


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