Novel oral administrated ellagic acid nanoparticles for enhancing oral bioavailability and anti-inflammatory efficacy

Abstract Ellagic acid (EA), a naturally occurring polyphenolic compound, is commonly known for its anti-inflammatory properties. The low bioavailability greatly limits the clinical applications of EA. In this study, a biodegradable hollow zein nanoparticle with an average diameter of about 70 nm was developed to mediate oral delivery of EA. The inner core of the nanoparticle consists of EA/sodium carbonate (EA/Na 2 CO 3 ) prepared by coprecipitation, which was further encapsulated in hollow zein nanoparticles with triethyl citrate as a natural plasticizer. The optimized ellagic acid-hollow plasticized zein nanoparticles (EA-HTZN) exhibited a small dimension of 72 nm with a PDI of 0.131, a drug loading capacity as high as 326  mg g −1 at an equilibrium concentration of 5.0  mg mL −1 . EA-HTZN had high drug loading and prevented their precipitation at simulated physiological environment. The EA-HTZN significantly improved permeation ability in vitro. Oral administration of EA-HTZN showed effective against inflammation related to suppression of pro-inflammatory cytokines (TNFα, IL1 β) overproduction in carrageenan-induced mouse paw edema model. Pharmacokinetic parameters of optimized formulation revealed 3.6- and 2.1-fold increase in bioavailability as compared to EA suspension and EA solid nanoparticle, respectively. Together, these results demonstrated the successful formulation of EA-HTZN and their potential to improve oral delivery through high drug loadings and good stability.