Novel self-nanomicellizing formulation based on Rebaudioside A: A potential nanoplatform for oral delivery of naringenin

In the study described here, we strove to develop an orally administered novel self-nanomicellizing formulation based on Rebaudioside A (RA) for delivering naringenin (NAR) with improved bioavailability and therapeutic efficacy. Our research found that RA and naringenin (NAR) could be formulated into self-assembling nanomicelles (RA-NAR) using a simple ethanol dissolution-evaporation method. We found that the RA-NAR self-assemblies comprised ultra-small micelles (5.234 ± 0.311 nm) in a uniform dispersion state (the polydispersity index was 0.243 ± 0.039) with a near-neutral surface charge (−[2.268 ± 0.729] mV). We also found that RA-NAR had a well-storage stability at 4 °C with light protection. In addition, we observed that RA-NAR exhibited enhanced apparent solubility, in-vitro permeability, and antioxidant activity. After we administered RA-NAR to rats orally, we observed an increase in area under the curve (AUC0→t) to 19,500.82 ng/mL/h versus 9324.47 ng/mL/h observed with free NAR and an increase of maximum concentration (Cmax) to 27,326.10 ng/mL from the free-NAR Cmax level of 2549.04 ng/mL. The tissue distribution assessments further demonstrated that RA-NAR could effectively increase the NAR concentration in all tested intestinal segments. Our mouse model results showed as well that oral administration of RA-NAR could efficiently protect against small intestine injuries induced by indomethacin, and the mechanisms by inhibiting proinflammatory cytokines and oxidative stress were involved in its therapeutic effect. Taken together, these findings indicate that a self-nanomicellizing formulation based on RA has great potential as a novel oral nano-drug delivery system for NAR. [Display omitted] •Self-nanomicellizing solid formulation based on Rebaudioside A (RA) was simply fabricated and this formulation could self-assembly form ultra-small micelles in aqueous solutions (particle size ~5 nm).•Self-nanomicellizing solid formulation based on RA dramatically improved oral bioavailability of naringenin and efficiently protected against small intestinal injury in a mouse model induced by indomethacin.•Self-nanomicellizing solid formulation based on RA could potentially be utilized as a green drug-delivery system, and this work would expand the research and application area of RA, a currently widely used noncaloric and natural sweetener.