Novel topical ophthalmic formulations for management of glaucoma

Preparation of topical ophthalmic formulations containing brimonidine-loaded nanoparticles prepared from various biodegradable polymers-PCL, PLA and PLGA-for sustained release of brimonidine as a once daily regimen for management of glaucoma.

Nanoparticles were prepared using spontaneous emulsification solvent diffusion method then characterized regarding their particle size, zeta potential, morphology and drug contents. Brimonidine-loaded nanoparticles were incorporated into eye drops, temperature-triggered in situ gelling system and preformed gel and characterized regarding their pH, viscosity, uniformity of drug contents, in vitro release study, in vitro cytotoxicity and in vivo intraocular pressure (IOP) lowering effects.

The results of optimized brimonidine-loaded PCL-, PLGA- and PLA-NPs respectively, are: particle sizes of 117.33 ± 4.58 nm, 125.67 ± 5.15 nm and 131.67 ± 3.79 nm; zeta potentials of -18.5 ± 2.87 mV, -21.82 ± 2.7 mV and -28.11 ± 2.21 mV; and encapsulation efficiencies of 77.97 ± 1.38%, 68.65 ± 3.35% and 73.52 ± 2.92%. TEM analyses revealed that all NPs have spherical shapes with dense core and distinct coat. In vitro release data showed a sustained release without any burst effect with Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are non-toxic. Also all formulations possessed a sustained IOP lowering effect compared to Alphagan® P eye drops.

Our formulations showed prolonged management of glaucoma that should meet with better patient compliance as a once-daily formulation.