Carmelo Puglia 1 2, Paolo Blasi 3, Carmine Ostacolo 4, Eduardo Sommella 5, Claudio Bucolo 6 7, Chiara B M Platania 6, Giovanni L Romano 8, Federica Geraci 6, Filippo Drago 6 7, Debora Santonocito 1, Barbara Albertini 9, Pietro Campiglia 5, Giovanni Puglisi 1 2, Rosario Pignatello 1 2
1Department of Drug Sciences, University of Catania, Catania, Italy. 2NANO-i – Research Centre on Ocular Nanotechnology, University of Catania, Catania, Italy. 3School of Pharmacy, University of Camerino, Camerino, Italy. 4Department of Pharmacy, University of Naples Federico II, Naples, Italy. 5Department of Pharmacy, University of Salerno, Fisciano, Italy. 6Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy. 7Center for Research in Ocular Pharmacology, University of Catania, Catania, Italy. 8Bascom Palmer Eye Institute, University of Miami Health System, Miami, FL, United States. 9Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
Abstract
Nanostructured lipid carriers (NLCs) loaded with palmitoylethanolamide (PEA) were formulated with the aim to enhance ocular bioavailability of PEA, particularly to the back of the eye. Technological characterization (e.g., size, charge) of NLC loaded with PEA formulation (PEA-NLC) was performed, and NLC morphology was characterized by electron microscopy. Ocular pharmacokinetic study, after topical administration of the formulation, was carried out in rabbit eye. Ultra-high performance liquid chromatography tandem mass spectrometry analysis was carried out to detect PEA levels in ocular tissues. Finally, the ocular tolerability of PEA-NLC formulation was assessed in rabbit eye. The novel formulation significantly increased PEA levels in ocular tissues compared to PEA suspension. Vitreous and retinal levels of PEA were significantly higher in the group treated with PEA-NLC formulation versus PEA suspension (PEA-NLC Cmax 5919 ± 541 pmol/g and 315 ± 70 pmol/g in vitreous and retina, respectively). The PEA-NLC formulation was characterized by high stability and robust ocular bioavailability. Therefore, this innovative formulation may be useful in clinical practice to manage retinal diseases.
Keywords: diabetic retinopathy; nanostructured lipid carriers; ocular drug delivery; palmitoylethanolamide; retinal diseases.