Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems

Abstract

The main inconvenience of conventional eye drops is the rapid washout of the drugs due to nasolacrimal drainage or ophthalmic barriers. The ocular drug bioavailability can be improved by either prolonging retention time in the cul-de-sac or by increasing the ocular permeability. The focus of this review is to highlight some chitosan-based drug delivery approaches that proved to have good clinical efficacy and high potential for use in ophthalmology. They are exemplified by recent studies exploring in-depth the techniques and mechanisms in order to improve ocular bioavailability of the active substances. Used alone or in combination with other compounds with synergistic action, chitosan enables ocular retention time and corneal permeability. Associated with other stimuli-responsive polymers, it enhances the mechanical strength of the gels. Chitosan and its derivatives increase drug permeability through the cornea by temporarily opening tight junctions between epithelial cells. Different types of chitosan-based colloidal systems have the potential to overcome the ocular barriers without disturbing the vision process. Chitosan also plays a key role in improving corneal wound healing by stimulating the migration of keratinocytes when it is used alone or in combination with other compounds with synergistic action.

Polysaccharides in Ocular Drug Delivery

“…Chitosan is another emerging polymer being considered for ophthalmic use [27,28]. Mucoadhesive chitosan formulations have been investigated as a strategy to overcome the rapid elimination of instilled ophthalmic solutions.…”

“…These positive charges are thought to interact with the negative charges of the ocular mucus, thereby enhancing bioadhesion. Chitosan formulations have shown promising results due to their significantly longer retention on the corneal surface when compared with conventional commercial ophthalmic solutions [27,29,30].…”

“…Mucoadhesion allows the drops to stabilize the tear film and prolong the residence time of ophthalmic drugs on the eye surface. Chitosan and some of its polycationic derivatives display mucoadhesion and promotion of ocular drug absorption via reversible permeabilization of the cornea [27]. This process has been utilized in further development of chitosan as component of nanoparticles and in-situ gelling systems [65].…”

“…Polysaccharides have been used to enhance the properties of ocular liposomes. Chitosan enhances the transcorneal permeability of drugs by disrupting the tight junctions in epithelial cellular sheets [27]. Coating of timolol-loaded liposomes with chitosan increased the apparent permeability coefficient of timolol by 2-3-fold when compared to timolol in solution and in uncoated liposomes.…”

Utilization of metabolic energy in treatment of ocular surface disorders: polyphosphate as an energy source for corneal epithelial cell proliferation

“…Those particles would provide a new formulation with adjustable release kinetics not only for the epithelial cells but also for the stabilization of the mucinous layer covering these cells on the eye surface. 58 In addition, this polymer would provide metabolic energy required for the regeneration of the corneal surface.…”