Cationic nanoemulsions with prolonged retention time as promising carriers for ophthalmic delivery of tacrolimus

Tacrolimus, also known as FK506, is a first-line drug for the topical treatment of immune-mediated inflammatory anterior ocular diseases (IIAODs). However, due to its limited water solubility, hydrophobic nature and relatively high molecular weight, topical application of FK506 features poor bioavailability. Numbers of formulations have been attempted to enhance the erratic bioavailability of FK506 through various techniques. But until now, none of them could satisfy the clinical needs completely. Here, a novel formulation of FK506, FK506-loaded cationic nanoemulsions (FK506 CNE), was developed to prolong the precorneal residence time of FK506, thereby enhancing the bioavailability of FK506 for IIAODs therapy. FK506 CNE was prepared by high-pressure homogenization, and its composition was screened and optimized by single-factor experiments. The FK506 CNE showed spherical morphology with a mean diameter of 178.8 ± 2.7 nm and a zeta potential of +25.6 ± 0.6 mV. Results from in vivo gamma scintigraphy studies proved that the precorneal residence time of FK506 CNE was significantly increased, compared with FK506-loaded neutral nanoemulsions (FK506 NE) and saline. The data of aqueous humor pharmacokinetic study in rabbits showed that the relative bioavailability of FK506 CNE was 1.68-fold and 1.77-fold of FK506 NE and the marketed FK506 eye drops (Talymus®), respectively. Finally, hematoxylin and eosin staining images and in vitro cytotoxicity data confirmed the safety of the FK506 CNE. Taking all these into consideration, we propose that FK506 CNE is a promising topical ophthalmic nanoformulation for the management of IIAODs. [Display omitted]