Sjögren's syndrome is a chronic systemic autoimmune disease affecting from 0.2 to 3% of the general population. The current treatment for Sjögren's syndrome is aimed at controlling symptoms such as dry eyes and xerostomia. Systemic therapy with glucocorticoids or immunosuppressants is also used. Baricitinib is an immunosuppressant drug, specifically a Janus kinases 1 and 2 selective inhibitor. We propose ocular liposomal formulations loaded with baricitinib for the management of Sjögren's syndrome. The novelty of the work relies on the fact that, for the first time, baricitinib is intended to be used for topical delivery. Two liposomal formulations were prepared with different lipids: (i) L-α-phosphatidylcholine (Lα-PC) and (ii) a combination of lipids 1-palmitoyl-2-oleoyl-phosphatidylethanolamine: s1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphoglycerol (3:1, mol/mol) (POPE:POPG), and they were physicochemically characterized. The in vitro drug release and the ex vivo permeation through corneal and scleral tissues were also assessed. Finally, the tolerance of the formulations on the ocular tissues was evaluated by the HET-CAM technique, as well as through the histological analysis of the cornea and sclera and the cornea transparency. Both liposomes resulted in small, spherical shapes, with suitable physicochemical properties for the ocular administration. Lα-PC led to higher flux, permeation, and retention in the sclera, whereas POPE:POPG led to higher flux and permeation in the cornea. The formulations showed no irritant effects on the chorioallantoic membrane. Additionally, the liposomes did not affect the cornea transparency when they were applied, and the histological analysis did not reveal any structural alteration.
Keywords: JAK inhibitor; Sjögren’s syndrome; baricitinib; liposomes; ocular delivery; ocular tolerance; transcorneal permeation; transscleral permeation.