In vitroandin vivoevaluation of ketotifen fumarate-loaded silicone hydrogel contact lenses for ocular drug delivery

Abstract

The purpose of this work was to evaluate the usefulness of silicone hydrogel contact lenses loaded with ketotifen fumarate for ocular drug delivery. First, silicone contact lenses were prepared by photopolymerization of bitelechelic methacrylated polydimethylsiloxanes macromonomer, 3-methacryloxypropyltris(trimethylsiloxy)silane, and N,N-dimethylacrylamide using ethylene glycol dimethacrylate as a cross-linker and Darocur 1173 as an initiator followed by surface plasma treatment. Then, the silicone hydrogel matrices of the contact lenses were characterized by equilibrium swelling ratio (ESR), tensile tests, ion permeability, and surface contact angle. Finally, the contact lenses were loaded with ketotifen fumarate by pre-soaking in drug solution to evaluate drug loading capacity, in vitro and in vivo release behavior of the silicone contact lenses. The results showed that ESR and ion permeability increase, and the surface contact angle and tensile strength decreased with the increase of DMA component in the silicone hydrogel. The drug loading and in vitro releases were dependent on the hydrogel composition of hydrophilic/hydrophobic phase of the contact lenses. In rabbit eyes, the pre-soaked contact lenses sustained ketotifen fumarate release for more than 24 h, which leads to a more stable drug concentration and a longer mean retention time in tear fluid than that of eye drops of 0.05%.

Synthesis and Characterization of Poly(2-hydroxyethylmethacrylate) Contact Lenses Containing Chitosan Nanoparticles as an Ocular Delivery System for Dexamethasone Sodium Phosphate

“…The authors observed no signs of discomfort in the animal models, though some of the eyes did develop corneal neovascularisation, which was possibly due to poor fitting lenses. In an earlier work, Xu et al also used rabbits to demonstrate in vivo release behaviour and for one of their contact lenses, observed no irritation or protein deposition [19]. The authors did, however, observe some lens deposition on another of their materials, again demonstrating the need for in vivo studies.…”

Delivery of Ketotifen Fumarate by Commercial Contact Lens Materials

“…1 The prevailing model of the pathogenesis of allergic conjunctivitis is sensitization of the ocular surface to specific antigens, such as pollen or dust, leading to proliferation of antigen-specific mast cells and the production of immunoglobulin E. 3 Upon subsequent exposure, the antigen binds to and triggers the cross-linking of a pair of immunoglobulin E antibodies located on the surface of conjunctival mast cells, ultimately causing the release of stored chemical messengers such as histamine, tryptase, leukotrienes, prostaglandins, cytokines, and platelet activating factor, all of which contribute to the signs and symptoms that characterize allergic conjunctivitis, including redness, swelling, and edema. [3][4][5] Ketotifen fumarate (KF) is a benzocycloheptathiophene derivative that is widely known to alleviate the signs and symptoms of SAC through multiple pharmacological actions. 4 It is a relatively small molecule, with the molecular weight (MW) of the ion being only 309.4 g/mol.…”

Development of Latanoprost-Loaded Biodegradable Nanosheet as a New Drug Delivery System for Glaucoma

“…7 Several novel drug delivery systems (DDSs) aimed at addressing the issue of adherence and ensuring consistent IOP reduction are under development. Various systems have been proposed, including contact lenses, [8][9][10][11] ocular inserts, 12,13 and injectable biodegradable micro-and nanoparticles. [14][15][16][17] The emergence of nanomaterials and nanometerorder devices that are applicable to ophthalmology is highly awaited.…”