Development of a Moxifloxacin Eluting Hydrogel Patch for Sealing Ocular Lacerations

Abstract

Purpose : Full thickness injuries, in particular full thickness lacerations, render the eye susceptible to infection and vision loss. They are particularly difficult to manage in low resource/emergency settings and repair typically requires extensive surgical skill with high frequency post-operative eyedrop regimens. To address these issues, we have developed a hydrogel sealant with the potential to be used as a rapid repair system to stabilize the globe for laceration type injuries while concurrently permitting sustained drug delivery of an antibiotic, Moxifloxacin (MFX), using a nanoparticle (NP) hydrogel system.

Methods : MXF NPs were synthesized and characterized using dynamic light scattering (DLS) to determine particle diameter (PD) and polydispersity index (PDI), and the encapsulation efficiency (EE) was determined. The sealant, composed of gelatin methacryloyl (GelMA) and glycidyl methacrylate-hyaluronic acid (HAGM), was characterized for degree of methacrylation (DM) and biocompatibility. Lastly, free MFX and MFX NPs were loaded into the hydrogel, and drug release profiles were determined via dialysis. Antimicrobial efficacy was assessed by zone of inhibition studies (ZOI) against a gram + (Staphylococcus Aureus; SA) and gram - (Pseudomonas Aeruginosa; PA) bacteria. The MFX NP hydrogel was further assessed in vitro for sealant capabilities via burst pressure testing.

Results : MFX NPs demonstrated a PD of 221 ± 11 nm, PDI of 0.21 ± 0.02, and EE of 93.8 ± 8.2%. Polymers exhibited a 61% and 11% DM for GelMA and HAGM, respectively, and no signs of cytotoxicity. The drug release profiles showed a 74.7 ± 2.38% and 29.65 ± 2.65% burst release within 2 h, with remaining MFX released within 24 h and 5 days respectively for hydrogels loaded with free MFX and MFX NPs. The MFX NP hydrogel demonstrated high antimicrobial efficacy with a ZOI > 30 mm against PA and > 28 mm for SA over 5 days. Lastly, the MFX NP hydrogel showed a high burst pressure of 40.8 ± 4.2 kPa.

Conclusions : The hydrogel sealant is capable of successfully loading NPs containing antibiotic which allows for efficacious levels of drug release for up to 5 days. Furthermore, it was highly adhesive and able to withstand high levels of pressure. Our drug eluting sealant has the potential to address critical factors in emergency ocular injury care by rapidly restoring the globe and concurrently allowing for efficacious levels of antibiotic to prevent infection.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.