A hypotonic gel-forming eye drop provides enhanced intraocular delivery of a kinase inhibitor with melanin-binding properties for sustained protection of retinal ganglion cells

2021 ◽  
Author(s):  
Yoo Chun Kim ◽  
Henry T. Hsueh ◽  
Matthew D. Shin ◽  
Cynthia A. Berlinicke ◽  
Hyounkoo Han ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Kinase Inhibitor ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Binding Properties ◽  
Melanin Binding

scholarly journals Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 647
Author(s):  
Henry T. Hsueh ◽  
Yoo-Chun Kim ◽  
Ian Pitha ◽  
Matthew D. Shin ◽  
Cynthia A. Berlinicke ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Rat Model ◽  
Kinase Inhibitor ◽  
Ganglion Cells ◽  
Corneal Neovascularization ◽  
Therapeutic Effects ◽  
Subconjunctival Injection ◽  
Retinal Ganglion ◽  
Drug Concentrations ◽  
Complementary Strategy

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

Calcium Signals Induced By Tonic Firing In Rat Retinal Ganglion Cells

2012 ◽  
Vol 3 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Kyril I. Kuznetsov ◽  
Vitaliy Yu. Maslov ◽  
Svetlana A. Fedulova ◽  
Nikolai S. Veselovsky
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Calcium Signals ◽  
Tonic Firing
Sign in / Sign up

Export Citation Format

Share Document