Enhanced Ophthalmic Drug Delivery: Mucoadhesive Mechanisms andClinical Potential of Novel Thiomer Nanoparticles

Introduction: Drug delivery to the eye is limited by fast tear clearance, low corneal permeability, and drainage. This leads to low drug levels and frequent dosing. While thiomerbased nanoparticles have been widely reported as mucoadhesive carriers, existing reviews largely describe their properties without critically integrating mechanistic insights with translational relevance. This review uniquely focuses on evaluating how thiomer nanoparticle engineering and mucoadhesive mechanisms can be strategically leveraged to advance clinically viable ophthalmic drug delivery systems. Methods: A thorough literature search of PubMed, Scopus, and Web of Science databases was done with the emphasis on research on thiomer nanoparticles, mucoadhesive drug delivery systems, and ophthalmic therapeutics. Beyond descriptive reporting, this review critically compares nanoparticle synthesis strategies, thiol-mediated mucoadhesion mechanisms, drug release behaviour, corneal penetration enhancement, and preclinical and emerging clinical evidence, identifying strengths, limitations, and knowledge gaps across studies. Results: Thiomer nanoparticles composed of thiolated polymers exhibit superior mucoadhesion through disulfide bond formation with ocular mucins, prolonging drug residence time. These nanoparticles enable sustained and controlled drug release, reducing dosing frequency and improving bioavailability for both hydrophilic and hydrophobic drugs. Additionally, ligandfunctionalized thiomers allow targeted delivery, minimizing systemic side effects. Discussion: Thiomers address key limits in eye drug delivery, such as short retention time and low uptake. Early studies support their use in glaucoma, dry eye, and eye infections. More work is needed on safety testing, large-scale production, and clinical use. Conclusion: Thiomers show strong promise for improving eye treatments and patient adherence. Further joint research is needed to move them from the lab into clinical care.