Hyaluronic Acid Modified Lutein Nanoparticles for Effective Application in Eye Drops: Development, Characterization, and Evaluation

Abstract

In this study, the possibility of using hyaluronic acid (HA) modified lutein as the main component of eye drops for ophthalmic treatment was discussed. Firstly, hyaluronic acid grafted lutein (HA-g-lutein) was synthesized by hydrophilic modification of lutein by Steglich esterification. The grafted copolymer was self-assembled in water to form micelles and then loading unreacted lutein to prepare composite nanoparticles (denoted HA-lutein NPs). The findings from the FTIR, UV–Vis, and XRD analyses indicate that the graft copolymers were synthesized while preserving the structural integrity of lutein. Furthermore, the modification demonstrated efficient inhibition of lutein crystallization. TEM showed that HA-lutein NPs self-assembled into spherical micelles in water, the particle size of which was on the nanometer scale. The saturation solubility of HA-lutein NPs exhibits a 48-fold increase compared to that of free lutein. Then the cytotoxicity of HA-lutein NPs and the effect on in-vitro transcorneal permeation of excised-rabbit cornea, corneal hydration level, and in-vivo ocular irritation after topical administration of HA-lutein NPs in rabbit eyes were studied. The results indicated the ocular safety of HA-lutein NPs. The quantitative analysis of permeability parameters by HPLC showed that the apparent permeability coefficient and the cumulative penetration quantity within 360 minutes of the HA-lutein NPs group were 3.71 and 7.04 times higher compared to the free lutein group. In summary, the graft modification of lutein with HA to form nanoparticles is an effective method to improve the availability of lutein in the eye and has potential application in ocular therapy.