Fabrication and Characterization of an Enzyme-Triggered, Therapeutic-Releasing Hydrogel Bandage Contact Lens Material

• Main Authors: Susmita Bose (Author), Chau-Minh Phan (Author), Muhammad Rizwan (Author), John Waylon Tse (Author), Evelyn Yim (Author), Lyndon Jones (Author)
• Format: Book
• Published: MDPI AG, 2023-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics16010026; 1999-4923
• Keywords: bandage contact lens; corneal wounding; gelatin methacrylate; GelMA+; MMP-9; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 16, Iss 1, p 26 (2023)

Purpose: The purpose of this study was to develop an enzyme-triggered, therapeutic-releasing bandage contact lens material using a unique gelatin methacrylate formulation (GelMA+). Methods: Two GelMA+ formulations, 20% <i>w</i>/<i>v</i>, and 30% <i>w</i>/<i>v</i> concentrations, were prepared through UV polymerization. The physical properties of the material, including porosity, tensile strain, and swelling ratio, were characterized. The enzymatic degradation of the material was assessed in the presence of matrix metalloproteinase-9 (MMP-9) at concentrations ranging from 0 to 300 µg/mL. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were evaluated using the AlamarBlue^TM assay and the LIVE/DEAD^TM Viability/Cytotoxicity kit staining with immortalized human corneal epithelial cells over 5 days. For drug release analysis, the 30% <i>w</i>/<i>v</i> gels were loaded with 3 µg of bovine lactoferrin (BLF) as a model drug, and its release was examined over 5 days under various MMP-9 concentrations. Results: The 30% <i>w</i>/<i>v</i> GelMA+ demonstrated higher crosslinking density, increased tensile strength, smaller pore size, and lower swelling ratio (<i>p</i> < 0.05). In contrast, the 20% <i>w</i>/<i>v</i> GelMA+ degraded at a significantly faster rate (<i>p</i> < 0.001), reaching almost complete degradation within 48 h in the presence of 300 µg/mL of MMP-9. No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days. However, the 30% <i>w</i>/<i>v</i> GelMA+ exhibited significantly higher cell viability (<i>p</i> < 0.05). The 30% <i>w</i>/<i>v</i> GelMA+ demonstrated sustained release of the BLF over 5 days. The release rate of BLF increased significantly with higher concentrations of MMP-9 (<i>p</i> < 0.001), corresponding to the degradation rate of the gels. Discussion: The release of BLF from GelMA+ gels was driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. This work demonstrated that a GelMA+-based material that releases a therapeutic agent can be triggered by enzymes found in the tear fluid.