Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment

Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects a...

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Bibliographic Details
Published in:Experimental eye research 2019-02, Vol.179, p.179-187
Main Authors: Cheng, Yung-Hsin, Ko, Yu-Chieh, Chang, Yu-Fan, Huang, Shu-Huei, Liu, Catherine Jui-ling
Format: Article
Language:English
Subjects:
Curcumin
Glaucoma
Latanoprost
Oxidative stress
Sustained release
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Summary:Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 μM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma. [Display omitted] •The eye drop formulation for dual drug delivery was developed and characterized.•The developed dual-drug delivery system showed a sustained release profile.•The developed formulation showed the both in-vitro and in-vivo biocompatibility.•The developed formulation decrease the inflammation and apoptosis levels of cells.•The developed formulation rescue TM cells from oxidative damage.
ISSN:0014-4835
1096-0007
DOI:10.1016/j.exer.2018.11.017