Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention

The mucoadhesive polysaccharide chitosan was evaluated as a potential compo nent in ophthalmic gels for enabling increased precorneal drug residence ti mes. This cationic vehicle was expected to slow down drug elimination by th e lacrymal Bow both by increasing solution viscosity and by interacting wit h the negative charges of the mucus. The molecular weight (M-W) and concent ration of polysaccharide were studied in four types of chitosan as paramete rs that might influence ocular tolerability and precorneal residence time o f formulations containing tobramycin as therapeutic agent. An ocular irrita tion test, using confocal laser scanning ophthalmoscopy (CLSO) combined wit h corneal fluorescein staining, clearly demonstrated the excellent toleranc e of chitosan after topical administration onto the corneal surface. Gamma scintigraphic data showed that the clearance of the formulations labelled w ith Tc-99m-DTPA was significantly delayed in the presence of chitosan with respect to the commercial collyrium (Tobrex(R)), regardless of the concentr ation and of the molecular weight of chitosan in solution. At least a 3-fol d increase of the corneal residence time was achieved in the presence of ch itosan when compared to Tobrex. (C) 1999 Elsevier Science B.V. All rights r eserved.