title: Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.
abstract: This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile.
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada.
authors.forename: Myrto
authors.initials: M
authors.lastname: Korogiannaki
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Guidi
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Lyndon
authors.initials: L
authors.lastname: Jones
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada School of Optometry and Vision Science, University of Waterloo, Waterloo, ON, Canada sheardow@mcmaster.ca.
authors.forename: Heather
authors.initials: H
authors.lastname: Sheardown
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D003263:Contact Lenses, Hydrophilic; D006820:Hyaluronic Acid / Q000032:analysis*; D020100:Hydrogels / Q000737:chemistry*; D012828:Silicones / Q000737:chemistry*; D013499:Surface Properties; D013999:Timolol / Q000008:administration & dosage*; D017155:Wettability
chemical_list: D000319:Adrenergic beta-Antagonists; D020100:Hydrogels; D012828:Silicones; D013999:Timolol; D006820:Hyaluronic Acid
keywords: Contact lens; hyaluronic acid; ocular drug delivery; polyvinylpyrrolidone; silicone hydrogel; timolol maleate; wetting agent