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Targeting the ocular surfaces and improving retention time are crucial to achieving high therapeutic outcomes for eye diseases. The most frequently used ophthalmic preparation is ocular drops, which, however, come with various limitations; therefore, advanced eye formulations are essential for the ocular medical field. Different methods, such as penetration enhancers, nanoparticles, ocular inserts, and lenses, have been utilized to improve the eye retention time. Although these formulations present limited advantages, combining them with surface-modified polymers can improve the therapeutic outcomes. Surface modification can be achieved through physical, chemical, and other methods. Chemical grafting is one of the most preferable methods, given that it is a straightforward methodology. This review summarizes the ocular microenvironment and eye barriers that should be overcome when designing ocular drug delivery systems. Most importantly, it summarizes ocular drug delivery systems based on surface-modified materials and emerging nanocarriers, also combined with IVT-mRNA therapeutics, offering promising advancements by enhancing targeting precision and therapeutic efficacy.
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