Hydrophobic vehicles for hydrophilic drugs: Sustained intravitreal caffeine delivery with oleogels.

Caffeine is the most widely consumed bioactive ingredient in the world, which has been found to show great therapeutic potential in several posterior eye diseases. While intravitreal injection represents the ideal administration route for these disorders, it remains challenging to achieve sustained release of caffeine in the vitreous. Herein, we address this issue by loading crystalline caffeine within oleogels (Ca@oleogels), oily delivery vehicles which provide a hydrophobic environment that is opposite to the hydrophilic nature of their cargos. Mathematical modeling of the in vitro release profiles indicated the diffusion process of the drug from Ca@oleogels was playing a dominating role in caffeine release. Furthermore, sustained intravitreal delivery was evidenced by higher drug levels from 12 h until the end of the pharmacokinetic study (240 h) and a 3.2-fold reduction in Cmax in Ca@oleogel dosed rabbits compared to their caffeine dosed counterparts. Superior therapeutic effects were obtained with Ca@oleogels in a laser-induced mouse choroidal neovascularization model. Advantages of Ca@oleogels as caffeine delivery vehicles included excellent biocompatibility, low cost and simplicity of manufacturing as well, which indicated they can be administrated safely and were readily amenable to scale-up production cost-effectively. Moreover, sustained release of another hydrophilic model drug (congo red) was also demonstrated with the same formulation design. Therefore, this strategy serves as a general solution to sustained intravitreal delivery of hydrophilic small molecule drugs.