Toward drug-driven design of topical ocular liposomes: a critical assessment of formulation decisions and ocular outcomes

Topical ocular liposomes are commonly judged by encapsulation efficiency, particle size and release, although these measures do not predict ocular performance without considering drug form, formulation and intended site of action. This structured narrative review examines topical ocular studies published between 2015 and 2026 identified through PubMed and Scopus searches conducted on 22 July 2026 and targeted citation tracing; earlier or non-topical evidence is used only to clarify formulation principles and limitations. It considers how condition-dependent solubility, ionization and lipophilicity informed loading, proposed intraliposomal localization, lipid and interface selection and ocular testing. Drug properties guided formulation hypotheses but did not independently predict encapsulation, release or ocular outcomes. Effects of cholesterol, charged components, coatings and ligands varied across drugs and formulations. Retention, deposition, permeation, ocular exposure, pharmacodynamic response and efficacy addressed distinct questions. Evidence for drug–lipid interactions was limited because formulation variables often changed together and drug location or binding was rarely measured. Progress is more likely to come from controlled, drug-specific comparisons than from increasingly complex liposomes. Studies should follow the drug from loading and release to the intended ocular endpoint while addressing stability, sterilization and manufacturability early. Unsupported assumptions should trigger reassessment of the earliest formulation decision.