|| Checking for direct PDF access through Ovid
We investigated if the self-assembled micelles of rebaudioside A (RA) could potentially be utilized as an ocular drug-delivery system in this investigation. RA self-assembled into micelles with ultra-small particle sizes (<4nm) in a homogeneous distribution state (polydispersity index<0.3). RA had good cellular tolerance and no cytotoxicity was observed at concentrations≤18.5mg/ml at 72h of incubation. RA also did not cause cell apoptosis at concentration≤12mg/ml. Coumarin-6 (Cou6)-loaded RA micelles had good cellular tolerance and in vivo non-irritants to the rabbit eyes. RA micelles dramatically improved the cellular uptake of Cou6 (compared to free-Cou6 P<0.05); an energy-independent, active, intracellular endocytosis pathway was apparently involved, and cellular organelles such as lysosomes, endoplasmic reticuli, and mitochondria were observed with a high distribution of Cou6, while a much more sophisticated endocytosis pathway was apparently involved in the ex vivo corneal endocytosis mechanism tests. The use of RA micelles significantly improved in vivo corneal permeation of the encapsulated Cou6 when compared to free-Cou6 eye drops (P<0.05). These findings indicate that RA micelle formulations have great potential as a novel ocular drug-delivery system to improve the bioavailability of hydrophobic drugs.