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Posterior capsule opacification (PCO) remains the most common cause of vision loss post cataract surgery. The clinical management of PCO formation is limited to either physical impedance of residual lens epithelial cells (LECs) by implantation of specially designed intraocular lenses (IOL) or laser ablation of the opaque posterior capsular tissues; however, these strategies cannot fully eradicate PCO and are associated with other ocular complications. In this review, we critically appraise recent advances in conventional and nanotechnology-based drug delivery approaches to PCO prophylaxis. We focus on long-acting dosage forms, including drug-eluting IOL, injectable hydrogels, nanoparticles and implants, highlighting analysis of their controlled drug-release properties (e.g., release duration, maximum drug release, drug-release half-life). The rational design of drug delivery systems by considering the intraocular environment, issues of initial burst release, drug loading content, delivery of drug combination and long-term ocular safety holds promise for the development of safe and effective pharmacological applications in anti-PCO therapies.