Hyaluronic-acid-modified lipid-polymer hybrid nanoparticles as an efficient ocular delivery platform for moxifloxacin hydrochloride.

To improve the ocular bioavailability of the strongly hydrophilic moxifloxacin hydrochloride, hyaluronic-acid-modified lipid-polymer hybrid nanoparticles (HA-LCS-NPs) were designed and characterized. An in vivo precorneal retention study in rabbits showed that the mean residence time (MRT) and area under the curve (AUC(0-6h)) of HA-LCS-NPs were up to 6.74-fold and 4.29-fold higher than those of the commercial product. An in vitro corneal penetration study in rabbits demonstrated that the apparent permeability coefficient (Papp) of HA-LCS-NPs was increased by 329-fold compared to the commercial product, which might be observed because the surface-modified hyaluronic acid could expedite the cellular uptake of HA-LCS-NPs by receptor-mediated endocytosis. Moreover, in contrast with other formulations, the results of ex vivo fluorescence imaging showed that the fluorescence intensity was higher in the cornea and conjunctiva after administration of HA-LCS-NPs. Finally, an ocular irritation study indicated that HA-LCS-NPs displayed excellent ocular tolerance. In summary, the hyaluronic-acid-modified lipid-polymer hybrid nanoparticles with multifunctional properties might be a promising ocular drug delivery system for prolonged precorneal retention, better corneal permeability and enhanced ocular bioavailability. (C) 2018 Published by Elsevier B.V.