Monoolein/phytantriol-enriched lipid-based nanocarriers loaded with resveratrol as topical ophthalmic vehicles: effect of PEGylation and incorporation in ophthalmic hydrogels and soft contact lenses

Abstract

Most topical ophthalmic solutions to treat posterior eye disorders demonstrate low therapeutic bioavailability. This results in poor medical outcomes and underlines the need for innovative non-invasive approaches. In this study, lipid-based nanocarriers (LN) of dioctadecyldimethylammonium bromide (DODAB) enriched with monoolein (MO@LN) or phytantriol (PHY@LN) were loaded with resveratrol (RSV-MO@LN/-PHY@LN) and functionalized with poly(ethylene glycol)2000–distearoyl-phosphatidylethanolamine (DSPE–PEG(2000)). PEGylated RSV-MO@LN/-PHY@LN exhibited favorable physicochemical properties for prolonged interaction with the ocular surface (>+30 mV) and enhanced permeation through ocular membrane barriers (76.3–113.8 nm; <0.3 polydispersity index). They also showed high RSV encapsulation efficiencies (92.1 ± 3.7–98.1 ± 0.7 %). Moreover, PEGylated RSV-MO@LN/-PHY@LN were incorporated in ophthalmic hydrogels (HG) and soft contact lenses (CL), and their influence on the vehicle's main parameters was assessed. HG exhibited non-Newtonian pseudoplastic rheological behavior, and the transmittance remained near 90 % in HG and almost all CL. Additionally, CL were characterized regarding their refractive index, equilibrium water content, central thickness, and power profiles, and did not show clinically relevant alterations. Furthermore, CL wettability and mechanical properties were studied, and the presence of PEGylated RSV-MO@LN/-PHY@LN within CL matrix was confirmed using ATR-FTIR and fluorescence microscopy. Finally, release studies highlighted the potential of PEGylated MO@LN/PHY@LN and HG/CL to enhance RSV release and promote its continuous delivery to the ocular cavity for several hours, compared to its non-encapsulated form. Altogether, PEGylated RSV-PHY@LN, incorporated either in HG or silicone hydrogel CL, seems to be a promising and innovative delivery strategy for ophthalmic applications.