Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment

Abstract

Inflammation plays a key role in dry eye disease (DED) affecting millions of people worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used topically to act on the inflammatory component of DED, but their limited aqueous solubility raises formulation issues. The aim of this study was development and optimization of functional cationic nanoemulsions (NEs) for DED treatment, as a formulation approach to circumvent solubility problems, prolong drug residence at the ocular surface and stabilize the tear film. Ibuprofen was employed as the model NSAID, chitosan as the cationic agent, and lecithin as the anionic surfactant enabling chitosan incorporation. Moreover, lecithin is a mixture of phospholipids including phosphatidylcholine and phosphatidylethanolamine, two constituents of the natural tear film important for its stability. NEs were characterized in terms of droplet size, polydispersity index, zeta-potential, pH, viscosity, osmolarity, surface tension, entrapment efficiency, stability, sterilizability and in vitro release. NEs mucoadhesive properties were tested rheologically after mixing with mucin dispersion. Biocompatibility was assessed employing 3D HCE-T cell-based model and ex vivo model using porcine corneas. The results of our study pointed out the NE formulation with 0.05 % (w/w) chitosan as the lead formulation with physicochemical properties adequate for ophthalmic application, mucoadhesive character and excellent biocompatibility.

Lipid Nanoparticle Technology for Delivering Biologically Active Fatty Acids and Monoglycerides

“…An eye drop formulation, which was composed of 0.25% MC, 1% hydroxypropyl methylcellulose, and 1% polysorbate 20, has also been developed and shown to kill N. gonorrhoeae bacteria in vitro and ex vivo [ 116 ]. Surfactant-containing microemulsions that incorporate LLA fatty acid are also being developed and have been shown to inhibit N. gonorrhoeae and S. aureus [ 117 ], while it would be advantageous to further explore other lipid-nanoparticle-based delivery platforms such as cationic nano-emulsions [ 118 ] and surfactant-free emulsions that could have improved performance and biocompatibility.…”

Ophthalmic Nanoemulsions: From Composition to Technological Processes and Quality Control

“…The chitosan-coated nanoemulsions were in turn produced by the addition of the chitosan solution to the aqueous phase before mixing and processing in a microfluidizer (1000 bar, 5 cycles). 69 …”

“… 69 , 83 , 87 Dukovski et al used atomic force microscopy in conjunction with fluorescence microscopy to determine the morphology of the dispersed phase in an ibuprofen-loaded cationic ophthalmic nanoemulsion. 69 Anjana et al used TEM to analyze the size and morphology of a curcumin-based ophthalmic nanoemulsion. The imaging was performed directly after drying a drop of 1:100 water diluted nanoemulsion deposited on the film grid.…”

Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments

“…Dukovski et al investigated the performance of a cationic nanoemulsion containing ibuprofen for the treatment of dry eye disease, in order to resolve ibuprofen solubility complications and stabilize the tear film [306]. Nanoemulsions were prepared by microfluidization, using lecithin as an anionic surfactant, Miglyol 812 as an internal oil phase, Kolliphor EL as the second surfactant, and CS.…”