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

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 gell...

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Detalles Bibliográficos
Autores principales: Kim, Yoo Chun, Shin, Matthew, Hackett, Sean, Hsueh, Henry T., e Silva, Raquel Lima, 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, Hanes, Justin, Ensign, Laura M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655548/
https://www.ncbi.nlm.nih.gov/pubmed/32895514
http://dx.doi.org/10.1038/s41551-020-00606-8
Descripción
Sumario: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, significantly 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 eyeball’s posterior segment in pigs. Our findings highlight the importance of formulations that conform to the ocular surface prior to viscosity enhancement, for increased and prolonged ocular-surface contact and drug absorption.