title: Stability and Ocular Pharmacokinetics of Celecoxib-Loaded Nanoparticles Topical Ophthalmic Formulations.
abstract: A spontaneous emulsification and/or solvent diffusion method was used for the preparation of celecoxib-loaded nanoparticles (NPs) using polymers, including chitosan (CS), sodium alginate, poly-ε-caprolactone (PCL), poly-l-lactide, and poly-d,l-lactide-co-glycolide. NPs were incorporated into vehicles (eye drops, in situ gelling system, and gel). Formulations were subjected to an accelerated stability study by storing them at elevated temperatures of 30, 35, and 45°C for 6 months. Formulations were evaluated monthly for general appearance, pH, viscosity, particle size, polydispersity index, zeta potential, and drug content. Gels containing CS-NPs and PCL-NPs were selected for an ocular pharmacokinetics study using Sprague-Dawley rats due to their high stability and long shelf lives (24.56 and 33.76 months, respectively). The gel improved NP stability by keeping it inside its network structure, which protected them from aggregation and interacting with water. Our formulations improved celecoxib bioavailability due to their bioadhesivness, thus preventing their rapid removal. Also, NPs acted as drug reservoirs that adhered to eye surface and continuously released the drug. The availability of celecoxib in all eye tissues and its absence in plasma suggests that our formulation could be used for anterior eye disorders and also for treatment of diseases associated with the posterior eye with no systemic side effects.
authors: Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee 38163; Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: Mohammed Mostafa
authors: MM
authors: Ibrahim
authors: Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: Abd-Elgawad Helmy
authors: AH
authors: Abd-Elgawad
authors: Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: Osama Abd-Elazeem
authors: OA
authors: Soliman
authors: Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee 38163; Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163. Electronic address: mjablonski@uthsc.edu.
authors: Monica M
authors: MM
authors: Jablonski
mesh_terms: D060433:Administration, Ophthalmic; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000068579:Celecoxib / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D004355:Drug Stability; D005123:Eye / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D000068579:Celecoxib
keywords: formulation; nanoparticles; pharmacokinetics; stability