title: Natural Bioadhesive Biodegradable Nanoparticle-Based Topical Ophthalmic Formulations for Management of Glaucoma.
abstract: OBJECTIVE
  We prepared and characterized topical ophthalmic formulations containing brimonidine-loaded bioadhesive cationic chitosan or anionic alginate nanoparticles (NPs) for sustained release of brimonidine as once daily regimen for management of glaucoma.
  
  
  METHODS
  Nanoparticles were prepared using a spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifiers, and NPs stabilizers were used for formulation optimization. Nanoparticles were characterized regarding particle size, zeta potential, morphology, and drug content. Brimonidine-loaded NPs were incorporated into eye drops, a temperature-triggered in situ gelling system, and a preformed gel. They then were characterized regarding their pH, viscosity, uniformity of drug content, in vitro release characteristics, in vitro cytotoxicity, and in vivo intraocular pressure (IOP) lowering effects.
  
  
  RESULTS
  Characteristics of optimized brimonidine-loaded chitosan and alginate NPs, respectively, are: particle size, 115.67 ± 3.58 and 157.67 ± 5.53 nm; zeta potential, +35.27 ± 3.39 and -37.8 ± 3.77 mV; encapsulation efficiency, 74.34% ± 2.05% and 70.40% ± 2.77%; drug loading, 11.81% ± 0.67% and 13.14% ± 0.90%; and yield, 87.91% ± 5.92% and 76.53% ± 3.32%. Transmission electron microscope (TEM) analyses revealed that NPs have spherical shapes with a dense core and distinct coat. Formulations possessed uniform drug content. Furthermore, pH and viscosity were compatible with the eye. Formulations showed a sustained release without any burst effect with a Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are biocompatible. Importantly, all formulations possessed a sustained IOP lowering effect compared to the marketed brimonidine tartrate eye drops.
  
  
  CONCLUSIONS
  These formulations provide a great improvement in topical ocular brimonidine delivery. The application of a single drop is sufficient to provide extended IOP reduction, which should improve patient compliance.
  
  
  CONCLUSIONS
  We have developed a novel biocompatible topical delivery system for brimonidine, a first line glaucoma medication. Once daily application should have positive effects on patient compliance and, therefore, preservation of vision.
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA ; Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Mohammed Mostafa
authors.initials: MM
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Abd-Elgawad Helmy
authors.initials: AH
authors.lastname: Abd-Elgawad
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Osama Abd-Elazeem
authors.initials: OA
authors.lastname: Soliman
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Jablonski
keywords: alginate; biocompatibility; brimonidine; chitosan; controlled release; cyctotoxicity; intraocular pressure; nanoparticles; ophthalmic