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Despite this potential, nanoparticle diffusion toward the visual axis can induce light scattering and visual disturbance. Given the negative charge of the vitreous, surface\u2010engineered nanoparticles provide a strategy to modulate particle mobility and restrict off\u2010target migration. Here, we performed a 6\u2010week in vivo evaluation in pigs of an intravitreally applied, positively charged, cyclic\u2010arginine surface\u2010functionalized liposomal nanocarrier designed to reduce intravitreal mobility. Three formulations containing 0.1%, 0.5%, or 1% cyclic\u2010arginine\u2010modified phospholipid were compared with unmodified control liposomes in a large animal pig model. A multimodal biocompatibility and performance assessment was conducted, including intraocular pressure monitoring, fundus imaging, structural and angiographic OCT, dye\u2010based angiography, and post\u2010mortem retinal immunostainings. Cyclic\u2010arginine surface functionalization of the liposomes resulted in a concentration\u2010dependent reduction in intravitreal mobility, quantified by vitreous haze and fundus\u2010based distribution analyses. All surface\u2010engineered nanoparticles demonstrated excellent ocular biocompatibility without structural or vascular adverse effects. These data establish cyclic\u2010arginine surface modification as a robust design principle to modulate intravitreal mobility and support the development of next\u2010generation nanoparticle biomaterials for long\u2010acting ophthalmic drug delivery.<\/jats:p>","DOI":"10.1002\/adhm.71531","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:35:45Z","timestamp":1785926145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering Concentration\u2010Dependent Intravitreal Mobility via Cyclic Arginine\u2010Enriched Nanocarrier Surface Modification: In Vivo Proof\u2010of\u2010Concept in a Porcine Large Animal Model"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5496-2537","authenticated-orcid":false,"given":"Maximilian","family":"Hammer","sequence":"first","affiliation":[{"name":"David J Apple Laboratory for Vision Research and University 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