Modification of timolol release from silicone hydrogel model contact lens materials using hyaluronic acid.

OBJECTIVES: The ability of hyaluronic acid (HA) to act as a functional additive in model silicone hydrogel contact lenses to alter the uptake and release characteristics of timolol was investigated. METHODS: Model contact lenses were prepared using 2 primary formulations: 2-hydroxyethyl methacrylate (HEMA) with 3-methacryloxypropyltris (trimethylsiloxy) silane (TRIS) in a 9:1 (wt:wt) ratio or N,N-dimethylacrylamide (DMA) with TRIS in a 1:1 (wt:wt) ratio. Ethylene glycol dimethacrylate (EGDMA) was used as the cross-linker. Four different model lens compositions were explored: unmodified controls, lenses containing HA, lenses that were molecularly imprinted with timolol maleate, and those that were both imprinted and contained HA. Model lenses were then used in subsequent materials characterization, drug loading, and drug release studies. RESULTS: Hyaluronic acid was shown to have the ability to act as a functional additive in these model contact lenses, significantly increasing the drug loading and release mass. This ability seemed to be independent of molecular imprinting, but its efficacy was related to the concentration of HA contained within model lenses and the concentration of drug loading solution used to facilitate uptake. Timolol release was sustained for a duration of approximately 2 days, and the dose of drug was shown to be controlled by both HA-drug interactions and molecular imprinting within the silicone hydrogels. CONCLUSIONS: Hyaluronic acid, although different than typical functional monomers used in molecular imprinting, can be a useful additive to modify the mass of drug release from model silicone hydrogel lenses.

Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

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.

The effect of silicone hydrogel contact lens composition on dexamethasone release.

The relationship between the delivery of dexamethasone and the composition of silicone hydrogel materials was investigated. Two hydrophilic monomers (2-hydroxyethyl methacrylate or N,N-dimethylacrylamide), a siloxy methacrylate-based monomer (1-(Bis(trimethylsiloxy)methylsilyl)propoxy-3-metacryloxy-2-propanol, a polysiloxane (monomethacryloxypropyl-terminated polydimethylsiloxane) and a polymerizable silicone surfactant (Silmer ACR A008-UP) were used to synthesize silicone hydrogels of variable composition. The materials properties, such as surface wettability and equilibrium water content, were highly dependent on polymer composition. All dexamethasone-loaded hydrogels showed uptake that was driven primarily by sorption to the polymer phase. Furthermore, a positive correlation between loading mass and equilibrium water content was established. The duration of drug release from the hydrogels ranged from one to greater than two weeks depending on the monomer composition and relative contribution of hydrophilic and hydrophobic monomers. Higuchi model rate constants for the release showed strong correlation with the equilibrium water content, signifying that the release is likely controlled by aqueous phase diffusion.