title: Effective Retinal Penetration of Lipophilic and Lipid-Conjugated Hydrophilic Agents Delivered by Engineered Liposomes.
abstract: Efficient delivery of drugs to the retina is critical but difficult to achieve with current methods. There have been a number of attempts to use intravitreal injection of liposomes, artificial vesicles composed of a phospholipid bilayer, to overcome the limitations of conventional intravitreal injection (short retention time, toxicity, poor penetration, etc.). Here, we report an optimal liposomal formulation that can diffuse through the vitreous humor, deliver the incorporated agents to all retinal layers effectively, and maintain them for a relatively long time. We first delivered lipophilic compounds and phospholipid-conjugated hydrophilic agents to the inner limiting membrane using engineered liposomes. Subsequently, the agents penetrated the retina deeply, presumably via extracellular vesicles, nanoscale vesicles secreted from retinal-associated cells. These results suggest that this engineered liposomal formulation can leverage the biological transport system for effective retinal penetration of lipophilic and lipid-conjugated agents.
authors.affiliation: Bora Eye Hospital, Gwang-ju 61964, Republic of Korea.
authors.forename: Junsung
authors.initials: J
authors.lastname: Lee
authors.forename: Unbyeol
authors.initials: U
authors.lastname: Goh
authors.forename: Hyoung-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Moonkyoung
authors.initials: M
authors.lastname: Jeong
authors.forename: Ji-Ho
authors.identifier: 0000-0002-0721-0428
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry; D012160:Retina / Q000187:drug effects* / Q000378:metabolism*; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010743:Phospholipids
keywords: drug delivery; extracellular vesicle; liposome; phospholipid; retina