Roles of effective stabilizers in improving oral bioavailability of naringenin nanocrystals: Maintenance of supersaturation generated upon dissolution by inhibition of drug dimerization

Nanocrystals (NCs), a colloidal dispersion system formulated with stabilizers, have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs. The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs. However, how stabilizers affect the bioavailability of NCs remains unknown. In this study, F68, F127, HPMC, and PVP were each used as a stabilizer to formulate naringenin NCs. The NCs formulated with PVP exhibited excellent release behaviors, cellular uptake, permeability, oral bioavailability, and anti-inflammatory effects. The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer, which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved. This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.