Novel ultrasmall nanomicelles based on rebaudioside A: A potential nanoplatform for the ocular delivery of pterostilbene

Rebaudioside A (RA) self-assembled into ultrasmall nanomicelles can be utilized as ocular drug delivery system; nevertheless, the therapeutic efficacy of RA micelles has not evaluated thus far. In this manuscript, the RA micelles are thought to strengthen the therapeutic effects of pterostilbene (Pt). Results showed that Pt can be highly encapsulated into RA micelles with ultrasmall particle sizes (3.99 ± 0.03 nm) with a uniform distribution (polydispersity index, PDI = 0.184 ± 0.008). RA-Pt exhibited pronounced improvement for the in vitro antioxidant activity and the in vitro membrane permeation of Pt. RA-Pt exhibited good ocular tolerance. The use of RA-Pt led to the significant improvement in the in vivo intraocular permeation of Pt as well as the improvement in the in vivo anti-inflammatory efficacy. The in vivo evaluation of antioxidant effects revealed that RA-Pt exhibits improvement in suppressing the generation of oxidative stress and inducing the enzymes of reactive oxygen species (ROS) degradation. Furthermore, RA-Pt was confirmed to exhibit a strong treatment efficiency for corneal alkali burns. These findings indicate that RA-based self-assembled ultrasmall nanomicelles demonstrate tremendous potential toward the improvement in the ocular bioavailability as well as a therapeutic effect of poor aqueous soluble drugs such as Pt.