Findings from a recent study published in Pharmaceutics outlined the development of an enzyme-triggered, therapeutic-releasing bandage contact lens (BCL) material using a unique formulation of gelatin methacrylate (GelMA+).
Give me some background first.
Traditionally, patients with corneal abrasions wear a clear, oxygen-permeable bandage contact lens for 3-7 days and instill topical antibiotics.
The main limitation of this approach is that current BCLs alone do not outperform ocular lubricants in terms of efficacy or speed of recovery because they lack the ocular surface factors or therapeutics to aid ocular surface repair.
So how was this BCL material developed?
Some background: Gelatin methacrylate (GelMA) and its derivatives can be biodegraded by matrix metalloproteinase (MMP) enzymes, which are elevated following a corneal wound—particularly MMP-2 and MMP-9.
A previous study demonstrated that GelMA could be converted to GelMA+, making the resultant gel eight times higher in mechanical strength and more suitable for high wear-tear applications, such as on the ocular surface.
Consequently, a research team from the University of Waterloo, Waterloo, Canada sought to evaluate the efficacy of an enzyme-triggered drug delivery system that releases a therapeutic when the GelMA+ gel is degraded by the MMPs present at the wound site on the cornea.
Now talk about the study.
In this study, investigators used ultraviolet (UV) polymerization to test two GelMA+ formulations: a 20% weight/volume (w/v) concentration and a 30% w/v concentration.
Researchers evaluated the physical properties of the GelMA+, including:
- Porosity
- Tensile strain
- Swelling ratio
- Cell viability
- Cell growth
- Cytotoxicity
Tell me more.
The enzymatic degradation of the material was assessed in the presence of MMP-9 at concentrations ranging from 0-300μg/mL.
For drug release analysis, the 30% w/v gels were loaded with 3μg of bovine lactoferrin (BLF) as a model therapeutic for wound healing, and its release was examined over 5 days under various MMP-9 concentrations.
Findings?
The 30% w/v GelMA+ formulation demonstrated (p<0.05):
- Higher crosslinking density
- Increased tensile strength
- Smaller pore size
- Lower swelling ratio
Conversely, the 20% w/v GelMA+ gel degraded at a significantly faster rate (p<0.001)—reaching almost complete degradation within 48 hours in the presence of 300μg/mL of MMP-9.
Keep going…
No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days.
However, the 30% w/v GelMA+ demonstrated significantly higher cell viability (p<0.05).
What about sustained-release drug delivery?
The 30% w/v GelMA+ exhibited sustained release of the BLF over 5 days, and the release rate of BLF increased significantly with higher concentrations of MMP-9 (p<0.001)—corresponding to the degradation rate of the gels.
Expert opinion?
As reported in the BLF release profile, according to the study authors, the release of the therapeutic agent was directly proportional to the presence of MMP-9—implying that the drug release corresponds to the wound’s severity.
Further, larger wounds would have higher MMP-9 levels, causing the GelMA+ to degrade faster, leading to a higher release of the therapeutic agents.
Limitations?
A key disadvantage of a GelMA+ BCL is that it would cause vision problems as it degrades, so this material would need to be incorporated as a contact lens skirt or ring implant.
Further, the material may need to be reformulated as an ocular insert that is placed under the lower lid, where slow degradation would not impact vision while releasing the therapeutic of interest.
Take home.
These findings suggest that the use of GelMA+ gels at different concentrations (20% and 30% w/v) may function as potential materials for therapeutic BCLs or ocular inserts to treat recurrent corneal erosion or other ocular surface injuries.
Next steps?
The study authors noted that further research is warranted to investigate approaches for optimizing the gel properties for increased degradation at lower, physiologically relevant MMP-9 concentrations.
And its future potential?
This technology could potentially be modified to treat not only eye injuries but large skin ulcers and other body sites that require targeted drug delivery as well.