Innovative thiomer technology ‐ application to dry eye syndrome

Abstract

AbstractPurpose Pre‐clinical and clinical studies were performed to study the safety and efficacy of a novel thiolated biopolymer, namely chitosan‐N‐acetylcysteine,. The mechanism of action is based on the interaction between thiol groups of the topically applied chitosan‐N‐acetylcysteine and cysteine‐rich mucin (MUC5AC). The hypothesis that this increases polymer residence time on the ocular surface and provides tear film stability was tested.Methods The efficacy of isotonic and buffered chitosan‐N‐acetylcysteine eye drops was studied in two different mouse models of dry eye disease. The dosage dependent ocular residence time and biodistribution were investigated in a rabbit model using microPET technology. Long‐term irritation and delayed‐type hypersensitivity tests with chitosan‐N‐acteylcysteine eye drop formulation were conducted in rabbits. Three phase one studies in healthy volunteers were performed to find an optimal dose and to test the safety of the formulation in humans.Results In mice treated with chitosan‐N‐acetylcysteine decreased expression of ocular surface mRNA of IL‐β, IL‐10, IL‐12α, and TNF was observed, indicating that the formulation decreases surface inflammation in models of dry eye. The residence time of chitosan‐N‐acetylcysteine eye drops on the ocular surface of rabbits was as high as 22h. Results of a long‐term ocular irritation study in rabbits demonstrate that chitosan‐N‐acetylcysteine was well tolerated and non‐irritant to the eye. In the phase I studies in healthy humans, safety and tolerability was demonstrated.Conclusion Safety and efficacy of chitosan‐N‐acetylcysteine was shown in different animal models. The long residence time of the polymer at the ocular surface makes it an attractive treatment approach for dry eye disease. Since the phase one studies showed a favourable safety profile in healthy subjects a phase two trial is planned in the near future.