Novel ophthalmic formulation of myriocin: implications in retinitis pigmentosa

Drug Deliv. 2019 Dec;26(1):237-243. doi: 10.1080/10717544.2019.1574936.

Abstract

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.

Keywords: Nanostructured lipid carriers; myriocin; ocular drug delivery; retinitis pigmentosa.

MeSH terms

  • Animals
  • Ceramides / metabolism
  • Chemistry, Pharmaceutical / methods
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / pharmacology*
  • Lipids / chemistry
  • Mice
  • Nanostructures / chemistry
  • Ophthalmic Solutions / chemistry
  • Ophthalmic Solutions / pharmacology*
  • Rabbits
  • Retina / drug effects*
  • Retina / metabolism
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / metabolism
  • Serine C-Palmitoyltransferase / metabolism
  • Sphingolipids / metabolism

Substances

  • Ceramides
  • Drug Carriers
  • Fatty Acids, Monounsaturated
  • Lipids
  • Ophthalmic Solutions
  • Sphingolipids
  • Serine C-Palmitoyltransferase
  • thermozymocidin

Grant support

This work was supported by “Piano Triennale per la Ricerca – Linea Intervento 2, University of Catania, Italy” (CB) and from the Research Center "Aldo Ravelli", University of Milan (RG). MDC is supported by the PhD program in Molecular and Translational Medicine of the University of Milan, Italy. The study was supported by the Fondazione Roma (ES).