Preparation and in vitro–in vivo evaluation of novel ocular nanomicelle formulation of thymol based on glycyrrhizin

[Display omitted] •Nanomicelle ophthalmic solution was developed with glycyrrhizin as nanocarriers.•This novel opthalmic formulation showed well in vivo ocular tolerance.•This opthalmic formulation displayed improved in vivo corneal permeation.•This formulation showed pronounced treatment efficacy of bacterial keratitis.•Glycyrrhizin contributed to a synergistic enhancement of the treatment efficacy. The development of an efficient ocular drug delivery system is helpful in improving the ocular diffusion of topically delivered drugs as well as enhancing drugs therapeutic efficacy. The objective of this study was to explore the potential of self-assembled nanomicelles based on glycyrrhizin in ocular topical applications. In brief, a dipotassium glycyrrhizinate (DG)-based nanomicelle ophthalmic solution encapsulating thymol (DG-THY) was developed using a simple thin-film dispersion method. The optimal formulation featured a DG/thymol (THY) weight ratio of 9:1 and an encapsulation efficiency of 98.25 ± 1.16%; the nanomicelles were ultra-small spheres with an average particle size of 3.30 ± 0.39 nm, a polydispersity index of 0.22 ± 0.02, and an electrically negative surface (-[10.03 ± 1.31] mV) for the optimized DG-THY. This DG-THY ophthalmic solution was observed to be stable upon good storage at both 4 °C and 25 °C for 12 weeks. The DG-THY was observed to remarkably improve in vitro antioxidant activity, in vitro release, and the membrane permeation of THY. The DG-THY ophthalmic solution proved to be very well-tolerated in a rabbit model. The DG-THY ophthalmic solution also demonstrated distinct improvements in the ex vivo and in vivo intraocular permeations of THY. The DG-THY ophthalmic solution also exhibited decreased minimal inhibitory concentrations and minimum bactericidal concentrations of THY. Treatment with the DG-THY ophthalmic solution significantly relieved ocular infection symptoms in rabbit eyes by lowering the number of colony-forming units recovered from the corneas. Therefore, these results demonstrate that DG-THY may be a promising new ophthalmic formulation for the treatment of ocular diseases, especially in terms of oxidative stress-, bacteria-, and inflammation-related eye diseases.