Enzyme-Triggered Therapeutic Embedded Into Bandage Contact Lenses Can Aid Corneal Healing

A therapeutic that detects enzymes in the tear film can be embedded into a soft bandage contact lens to help heal corneal wounds.

For soft bandage contact lenses, researchers have developed an enzyme-triggered therapeutic release platform utilizing a gelatin methacrylate formulation (GelMA+) and bovine-lactoferrin (BLF), according to a study presented at the American Academy of Optometry 2022 annual meeting, held in San Diego from October 26 to October 29, 2022. 

Study author Lyndon Jones, PhD, et al, prepared 2 formulations of GelMA+, 20% and 30% weight/volume, using UV polymerization. They characterized the properties of the material, such as porosity, tensile strain, and swelling. The degradation of GelMA+ in the presence of matrix metalloproteinase-9 (MMP-9), usually found upregulated at a wound site, from 0 to 300 µg/mL of the enzyme was also assessed. 

The investigators determined cell viability, cell growth, and cytotoxicity on the GelMA+ gels by using the AlamarBlueTM assay and the LIVE/DEAD™ Viability/Cytotoxicity Kit staining with immortalized human corneal epithelial cells after 5 days. In the preliminary drug release study, the 30% GelMA+ gels were also loaded with 3 µg of BLF, and the release of the therapeutic was assessed over 5 days at different MMP-9 concentrations (0, 100, 300 µg/mL) in phosphate-buffered saline (PBS 1X) at 37° C. 

Researchers washed the gels for 1 hour at room temperature (22–24° C) prior to the release phase to remove any loosely bound BLF on the surface. They measured the amount of BLF released using an ELISA kit and UV absorbance at 450 nm. 

The researchers found that the 30% weight/volume GelMA+ had a higher crosslinking density, tensile strength, smaller pore size, and lower swelling ratio compared with the 20% weight/volume GelMA+ (P <.05). They observed that the degradation rate of the 20% weight/volume gel was significantly faster (P <.001), almost completely degrading after 48 hours at 300 µg/mL of MMP9. After 5 days, the team identified no cytotoxicity in the live/dead staining for either concentration. However, the 30% weight/volume GelMA+ demonstrated significantly higher cell viability (P <.05). 

In the drug release study, the researchers observed no burst release of BLF for the 30% weight/volume gel, and the release of the therapeutic was sustained over 5 days, according to the report. They found that the rate of release from the gel significantly increased with increasing concentrations of MMP-9 (P <.001), associated with the rate of degradation of the gels.

“The results showed that degradation of GelMA+ can be tuned by modifying the cross-linking density or exposure to different concentrations of MMP-9,” according to the presenters. “The release of BLF from 30% GelMA+ is driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. Future work will focus on optimizing the materials to deliver other therapeutic agents at physiologically-relevant concentrations of MMP enzymes found in the tear fluid.”

References:

Jones L, Bose S, Phan C-M, Rizwan M, Tse JW, Yim E. Fabrication of an enzyme-triggered therapeutic releasing biomaterial for bandage contact lenses. Poster presented at: American Academy of Optometry 2022 annual meeting; October 26-29, 2022; San Diego, CA.