Novel ophthalmic formulation of myriocin: implications in retinitis pigmentosa

Drug Delivery

Enrica Strettoi¹  Chiara Bianca Maria Platania²  Francesca Lazzara²  Annamaria Fidilio²  Claudio Bucolo³  Filippo Drago³  Rita Paroni⁴  Riccardo Ghidoni⁴  Michele Dei Cas⁴  Simona Cianciolo⁵  Rosario Pignatello⁶ 

[1] CNR Neuroscience Institute, Pisa, Italy;Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy;Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy;Center for Research in Ocular Pharmacology-CERFO, University of Catania, Catania, Ital;Department of Health Sciences, University of Milano, Milano, Italy;Drug Sciences Department, University of Catania, Catania, Italy;Drug Sciences Department, University of Catania, Catania, Italy;NANO-i – Research Center on Ocular Nanotechnology University of Catania, Catania, Italy;

关键词: Nanostructured lipid carriers;    ocular drug delivery;    myriocin;    retinitis pigmentosa;   

DOI  :  10.1080/10717544.2019.1574936

来源: publisher

【 摘 要 】

Myriocin is an antibiotic derived from Mycelia sterilia, and is a potent inhibitor of serine palmitoyltransferase, the enzyme involved in the first step of sphingosine synthesis. Myriocin, inhibiting ceramide synthesis, has a great potential for treatment of diseases characterized by high ceramide levels in affected tissues, such as retinitis pigmentosa (RP). Drug delivery to the retina is a challenging task, which is generally by-passed through intravitreal injection, that represents a risky invasive procedure. We, therefore, developed and characterized an ophthalmic topical nanotechnological formulation based on a nanostructured lipid carrier (NLC) and containing myriocin. The ocular distribution of myriocin in the back of the eye was assessed both in rabbits and mice using LC-MS/MS. Moreover, rabbit retinal sphingolipid and ceramides levels, after myriocin-NLC (Myr-NLC) eye drops treatment, were assessed. The results demonstrated that Myr-NLC formulation is well tolerated and provided effective levels of myriocin in the back of the eye both in rabbits and mice. We found that Myr-NLC eye drops treatment was able to significantly decrease retinal sphingolipid levels. In conclusion, these data suggest that the Myr-NLC ophthalmic formulation is suitable for pharmaceutical development and warrants further clinical evaluation of this eye drops for the treatment of RP.

【 授权许可】

CC BY