Project Description: INTRODUCTION:
Allergic conjunctivitis affects nearly 40% of the North American population. Topical eye drops are the most common treatment method, but it is generally accepted that less than 5% of an applied dose remains bioavailable, resulting in frequent reapplication. We tested the hypothesis that the incorporation of a chitosan crosslinker into thermo-sensitive polymeric hydrogels would yield a superior eyedrop formulation with a longer duration of action, capable of overcoming current dosing issues.
METHODS: For anterior application, novel N-ispropylacrylamide (NIPAAm) based, thermo-sensitive hydrogels were synthesized incorporating two co-monomers. Hydrophobic methyl methacrylate (MMA) was added to control gelation temperature and acrylic acid (AA) was incorporated for chemical crosslinking with chitosan. The terpolymer (pNAM) compositions were determined by nuclear magnetic resonance (NMR) and the size of the polymers by gel permeation chromatography (GPC). Chitosan properties and co-monomer concentrations are optimized to yield a system with the desired thermo-gelling, mechanical, biodegradable and drug releasing properties. For enzymatic degradation quantification, the hydrogels were incubated with simulated tear fluid and the dry mass of the hydrogel was measured at given time intervals. Release of the anti-allergy drug ketotifen was assessed by high performance liquid chromatography (HPLC).
RESULTS: By incorporating chitosan through charge or by covalent bonding the degradation profile of the gels can be tailored from one to several days. Importantly the degradation profiles were not influenced by the presence of lysozyme suggesting the mechanism of degradation is swelling rather than enzymatic digestion.
DISCUSSION/CONCLUSIONS: A chitosan crosslinked thermogel has been synthesized and was optimized to control drug release while maintaining the desirable physical properties. This system has the ability to overcome the practical dosing limitations that are seen within the allergic conjunctivitis industry. The drug delivery platform is versatile and may be used to also treat other anterior conditions.