Hyaluronic acid in silicone hydrogels shows promise for ocular drug delivery

The lenses could provide another option for treating both anterior and posterior segment disease.

Issue: July 2012

Researchers found that using hyaluronic acid in silicone hydrogels to help control the release of hydrophobic drugs resulted in an increase in both the amount and the duration of the drug released.

“While contact lenses have been widely used for decades, and the use of contact lenses for delivering drugs has been of interest for almost as long, the development of an efficacious system has been difficult,” Heather Sheardown, PhD, one of the study’s authors, said in an interview with Primary Care Optometry News. ‘The results of this study demonstrate that it is possible, with certain drugs, to use the embedded hyaluronic acid to control drug release.”

The silicone hydrogels (SHs) used in this study were modified to consist of one of two hydrophilic monomers, either hydroxyethyl methacrylate or N,N-dimethylacrylamide (DMAA), a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane (TRIS) and hyaluronic acid (HA) (7.5 kDa). In addition, ethylene glycol dimethacrylate (EGDMA) was used as the cross-linker and atropine as the model hydrophobic drug. Primary outcomes were measurements for surface hydrophilicity and equilibrium water content (EWC) for the modified SH.

Heather Sheardown

The swelling study showed that the incorporation of HA significantly increased the EWC of drug-loaded DMAA/TRIS hydrogels. Also, as the advancing contact angles were decreased, the presence of HA in the drug-loaded DMAA/TRIS materials improved the surface hydrophilicity of the hydrogels. Atropine was released for more than 2 weeks, and the incorporation of HA during synthesis led to an increase in the amount and the duration of the drug released, according to the study.

“The ability to treat ocular diseases over a more prolonged period of time has significant potential — for treating diseases of both the front and back of the eye,” Dr. Sheardown said. “It may be possible that extended contact of the drug on the eye will lead to the potential for posterior segment treatments.”

Dr. Sheardown was also involved in a related study that analyzed data derived from the use of a molecular imprinting polymerization strategy to slow diffusion of timolol and HA in novel hydrogel materials.

This study found that the polarity of monomers, the ratio of their contribution and the nature of their therapeutic effect were all determining factors in the system’s uptake and release, which, as observed in the study, 90% of the drug released over a 2- to 3-day period. Also, materials applied with both timolol and HA had the longest release durations, as opposed to those applied with timolol alone.

“Hyaluronic acid imprinting appears to affect the uptake and release of therapeutics regardless of its similarity to the target compound, and this interaction requires further characterization,” the study authors said. “The increase in uptake affinity associated with timolol-imprinted materials is consistent with established literature; however, the effect of HA increasing drug release is a novel result.”

Dr. Sheardown commented: “While it is difficult to predict how long it will be before such a system is used clinically — because eye drops are so well accepted — there is precedent, and should an effective system be developed with commercially available materials, moving it to a patient population is possible in a relatively short time frame … 5 years or less, optimistically.”

Addressing potential resistance to this concept from legislative bodies, Dr. Sheardown said she did not expect it would be an issue. “Contact lenses are approved for wear for up to 30 days, so this time frame fits well with the need for extended drug delivery.”– by Daniel R. Morgan

References:

Guidi G, Weeks AK, Sheardown H. Molecularly imprinted hydrogels with hyaluronic acid for ocular drug delivery. Paper presented at: Annual Meeting of the Association for Research in Vision and Ophthalmology; March 15, 2012; Fort Lauderdale, FL.
Korogiannaki M, Sheardown H. Hyaluronic acid-containing silicone hydrogels: their use as extended drug delivery systems of hydrophobic ocular drugs. Paper presented at: Annual Meeting of the Association for Research in Vision and Ophthalmology; March 15, 2012; Fort Lauderdale, FL.

For more information:

Heather Sheardown, PhD, can be reached at McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L7; (905) 525-9140 ext. 24794; sheardow@mcmaster.ca.
Disclosures: Dr. Sheardown has no relevant financial interests to disclose.