Pharmaceutical treatment for glaucoma, an ocular illness characterized by elevated intraocular pressure (IOP), is hindered by challenges like limited bioavailability of drugs and difficulties in corneal delivery due to the human eye’s unique anatomy. This research investigated the efficiency of liquid crystal nano cubosomes containing Dorzolamide and Timolol as a corneal drug delivery system. We used glycerol monooleate (GMO) and poloxamer 407 to prepare Dz/TM cubosomes. The mixture was stirred, homogenized, and probed. Dynamic light scattering (DLS) was used to evaluate the size, PDI, and zeta potential of cubosomes, and their physicochemical properties, phase behavior, in vitro release kinetics, cytotoxicity, and pharmacodynamic and pharmacokinetic features were also investigated. The average size, zeta potential, and PDI of the cubosomes were 143.5 ± 2.3 nm, ???? 26.3 ± 1.7 mV, and 0.164 ± 0.014, respectively. Drug encapsulation efficiency was 84.5 ± 2.1 % for Dz and 91.3 ± 2.7 % for TM. In vitro release testing showed a slow-release pattern for both Dz and TM reaching the maximal dose after 24 h. In vivo evaluations showed a considerable reduction in IOP from 27.28 to 19.40 within 4 h of administration and an increase in the retention time of both drugs. Pharmacokinetic studies revealed that cubosomes had longer bioavailability than Zilomole®, and Dz/TM cubosomes offered higher areas under the curve (AUC) for both drugs compared to available marketed eye drops. The prepared formulation led to no significant histopathological damage to the cornea, indicating its optimal biocompatibility. Overall, this formulation seems to be a safe constant-release drug carrier to deliver medications to the cornea.

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