Assessing liposomal compositions for posterior ocular therapeutics: revelations from animal model research—a systematic review

Despite advances in retinal therapeutics, drug delivery remains hindered by ocular barriers and rapid clearance. Liposomes provide a promising strategy due to their capacity to enhance drug retention, protect labile compounds, and enable targeted delivery to the retina. Conventional eye drop formulations are inadequate for sustained retinal delivery, highlighting the need for optimized nanocarriers. Our systematic review examined how variations in liposomal composition influence drug delivery efficiency in posterior segment eye diseases. <i>In vivo</i> and <i>ex vivo</i> studies published until November 11, 2025 were systematically searched in PubMed-MEDLINE and SCOPUS. Fourteen studies were included, focusing on liposome preparation methods, particle size, and ocular targeting. Risk of bias (ROB) was assessed using the SYRCLE tool, and the review adhered to PRISMA 2020 guidelines (protocol registered in PROSPERO: CRD42024513400). Findings indicated that lipid-to-cholesterol ratios, surface modifications, and polymer coatings substantially affected particle size, encapsulation efficiency, and drug bioavailability at the retina. While these modifications improved therapeutic outcomes, challenges persist in achieving sustained release and clinical reproducibility. ROB assessment revealed methodological limitations across studies. Due to heterogeneity, we performed semi-quantitative weight-of-evidence data correlation to compare the studies. Standardizing formulation strategies and preparation protocols is essential. Future research should prioritize optimized lipid compositions and noninvasive delivery methods to enhance retinal penetration and retention.