Natural biomaterials for contact lens-based ophthalmic drug delivery systems

Effective treatment of ocular diseases remains challenging due to the limitations of conventional eye drop formulations, such as low bioavailability, rapid drug clearance, and poor patient compliance. Contact lenses offer a promising alternative for sustained ocular drug delivery, providing extended drug retention and enhanced therapeutic outcomes. However, traditional contact lenses made from synthetic polymers have significant limitations, including low drug-loading capacity, uncontrolled release profiles, and protein adsorption. These challenges underscore the need for advanced materials, particularly natural biomaterials, to improve drug delivery properties and ocular compatibility. Natural biomaterials, derived from renewable biological sources, offer significant advantages including biocompatibility, biodegradability, minimal immunogenicity, wettability, and favorable patient comfort. To this end, this review comprehensively explores various natural polymers such as chitosan, alginate, hyaluronic acid, gelatin, collagen, silk fibroin, and cyclodextrin utilized in fabricating drug-loaded contact lenses. Particular emphasis is given to material properties, contact lenses formulation methods, drug loading techniques, and physicochemical properties. Furthermore, existing challenges including scalability of production and clinical translation barriers are discussed. Future directions are proposed to encourage research toward developing advanced biomaterial-based lenses capable of responsive and targeted ocular drug delivery. Overall, natural biomaterials represent a transformative approach, offering significant potential to improve ocular drug therapies and patient quality of life.