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.