Dusane, Apurva1; Skeie, Jessica M.2; Shevalye, Hanna3; Eggleston,Tim3; Kalidindhi,Swathi1; Okafor, Cynthia1; Schmidt, Gregory A.3; Salem, Aliasger K.1; Greiner,Mark A.2
Departments of 1Pharmaceutical Sciences and Experimental Therapeutics; 2Ophthalmology and Visual Sciences, University of Iowa; 3Iowa Lions Eye Bank
Purpose: Currently, surgical procedures are the only first line treatment for Fuchs endothelial corneal dystrophy (FECD). We aimed to develop a rho-kinase inhibitor nanomedicine approach for targeting corneal endothelial cells (CECs) to prevent FECD progression. Rho-kinase inhibitor comprising nanoparticulate eye drops were used.
Methods: Nanoparticles were characterized by measuring size and charge using Zetasizer. Drug loading and encapsulation efficiency were quantified using HPLC-DAD. Particles were characterized using XRD. Formulation stability was examined for 2 months at 4°C and 25°C. Release studies were performed at 37°C. Safety and Efficacy of formulation was evaluated on mice with a well-characterized FECD mutation (129S6/SvEvTac Col8a2Q455K). Optical coherence tomography (OCT) and confocal imaging were performed to study progression of guttae and changes in CEC morphology. An initial baseline for these techniques on a mouse cohort was recorded at the age of 4 months, then subsequently after 1 month of therapy (age of 5 months) and after 2 months of therapy (age of 6 months).
Results: Particle size was determined to be 81.60± 2.48 nm with a narrow polydispersity index (PDI) (n = 3 batches). XRD indicated drug incorporation in nanoparticles. Formulation exhibited in vitro controlled drug release. In the mouse model, the nanoparticulate drug therapy had a good safety profile and low off-target side-effects. CCM indicated an overall improvement in cell health with RKI nanoparticle treatment.
Conclusions: Findings indicate the successful development of rho-kinase targeted nanoparticles as a possible drug delivery strategy for CECs to prevent FECD progression.
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