Gelling hypotonic polymer solution for extended topical drug delivery to the eye

• Published in: Nature biomedical engineering Vol. 4; no. 11; pp. 1053 - 1062
• Main Authors: Kim, Yoo Chun, Shin, Matthew D., Hackett, Sean F., Hsueh, Henry T., Lima e Silva, Raquel, Date, Abhijit, Han, Hyounkoo, Kim, Byung-Jin, Xiao, Amy, Kim, Youngwook, Ogunnaike, Laolu, Anders, Nicole M., Hemingway, Avelina, He, Ping, Jun, Albert S., McDonnell, Peter J., Eberhart, Charles, Pitha, Ian, Zack, Donald J., Campochiaro, Peter A., Hanes, Justin, Ensign, Laura M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2020; Nature Publishing Group
• Subjects: 639/166/985; 692/308/575; Absorption; Administration, Topical; Animals; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Blinking; Block copolymers; Clumps; Drug delivery; Drug Delivery Systems - methods; Epithelium; Eye; Eye - diagnostic imaging; Eye - drug effects; Female; Gels - administration & dosage; Gels - chemistry; Hydrophobicity; Hypotonic Solutions - administration & dosage; Hypotonic Solutions - chemistry; Male; Mice, Inbred C57BL; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Ophthalmic Solutions - administration & dosage; Ophthalmic Solutions - chemical synthesis; Polymers; Polymers - administration & dosage; Polymers - chemistry; Rabbits; Rats, Sprague-Dawley; Resists; Surface chemistry; Swine; Tears; Topical application
• ISSN: 2157-846X; 2157-846X
• DOI: 10.1038/s41551-020-00606-8

Eye-drop formulations should hold as high a concentration of soluble drug in contact with ocular epithelium for as long as possible. However, eye tears and frequent blinking limit drug retention on the ocular surface, and gelling drops typically form clumps that blur vision. Here, we describe a gelling hypotonic solution containing a low concentration of a thermosensitive triblock copolymer for extended ocular drug delivery. On topical application, the hypotonic formulation forms a highly uniform and clear thin layer that conforms to the ocular surface and resists clearance from blinking, increasing the intraocular absorption of hydrophilic and hydrophobic drugs and extending the drug–ocular-epithelium contact time with respect to conventional thermosensitive gelling formulations and commercial eye drops. We also show that the conformal gel layer allows for therapeutically relevant drug delivery to the posterior segment of the eyeball in pigs. Our findings highlight the importance of formulations that conform to the ocular surface before viscosity enhancement for increased and prolonged ocular surface contact and drug absorption. A gelling hypotonic solution for ocular delivery that forms a uniform and clear thin layer conformal to the ocular surface resists clearance from blinking and extends the residence time of the delivered drugs.