Mucoadhesive nano-sized supramolecular assemblies for improved pre-corneal drug residence time

Abstract

Context: Mucoadhesive nanoparticles were compared with non-aggregated constituent polymers for effect on pre-corneal residence of dexamethasone phosphate (DP) or met-enkephalin (ME), administered by eye-drops to rabbits.

Objective: Deepening the knowledge of ophthalmic nanoparticulate systems in terms of ability to prolong pre-corneal residence.

Materials and methods: Medicated nanoparticles resulted from gelation of quaternary ammonium–chitosan conjugate or its thiolated derivative with hyaluronan in the presence of drug. Particles were analyzed by light scattering. Dialysis removed non-encapsulated drug, dynamic dialysis measured drug–polymer interactions, and lyophilization-stabilized product. Dispersions were regenerated from lyophilized products. Also solutions of non-thiolated or thiolated chitosan derivative were administered. Mean drug residence time (MRT) in tears was determined by collecting samples from lower marginal tear strip of albino rabbits using capillaries.

Results and discussion: Nanoparticle size of regenerated dispersions was 400–430?nm (DP-systems), 360–370?nm (ME-systems); the drug content was 2.5?mg/mL (DP) or 0.3?mg/mL (ME). The MRT for DP nanoparticles from non-thiolated derivative was higher than that for non-aggregated polymer, due to stronger concurrent interactions of positively charged nanoparticles with ocular surface and drug. Thiolated polymer nanoparticles and non-aggregated parent polymer, both interacting weakly with DP, showed similar MRT values. The MRT of ME could only be enhanced by protecting drug from enzymatic hydrolysis. This was done by nanoparticle systems, whereas non-aggregated polymers were ineffective.

Conclusion: Developing a nanoparticle system rather than a solution of mucoadhesive polymer, for prolonging pre-corneal residence, is convenient, provided nanoparticles interact strongly with both ocular surface and drug, or protect drug from metabolic degradation.