Abstract
Purpose :
Topical eye drops, the current industry standard for anterior drug delivery, is limited with about 5% of the drug remaining on the target site after 5 minutes. This leads to the need for frequent dosing and high drug concentrations. It has been shown that targeting the mucin layer of the tear film can enhance drug residence time. In this study, different variations of a mucoadhesive polymer were synthesized. In order to create a mucoadhesive drug, the polymer was conjugated to a cell adhesion peptide and a model antibiotic drug. The system was characterized to determine the chemical, physical, and biological properties of the materials.
Methods :
A copolymer comprised of a negatively charged acrylic acid (AA) monomer and a mucoadhesive 3-acrylamidophenylboronic acid monomer (PBA) was synthesized. The polymer was tethered to RGDS peptide as well as to vancomycin as a model antibiotic drug. The polymer-drug conjugates were characterized using 1H NMR and gel permeation chromatography (GPC). The rheological and mucin binding properties of the polymer dissolved in phosphate buffered saline were tested using a rheometer and surface plasmon resonance (SPR), respectively. To assess safety and tolerability in vitro, immortalized human corneal epithelial cells were exposed to the polymer and the viability tested via MTT assay. To confirm antimicrobial properties of the antibiotic, a streptococci bacterial strain was used.
Results :
Successful polymerization and conjugation were confirmed using 1H NMR and GPC. Rheology confirmed the polymer was capable to be delivered via eyedrop, while mucin affinity was verified using a mucin binding assay with SPR. Cell viability of the blank polymer and polymer-drug conjugate were established, demonstrating the safety and tolerability of the polymer. Increased cellular activity shown via MTT suggested the model RGDS peptide remained active when conjugated. Polymer-bound drug remained active against streptococcus bacteria when conjugated.
Conclusions :
A mucin binding polymer was developed which could be tethered to a model drug compound. The polymer-drug conjugate showed mucin binding properties as well as suitable rheological properties. Ongoing work is aimed as assessing the impact of the mucoadhesive drug in vivo.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.