Gamma oryzanol loaded into micelle-core/chitosan-shell: from translational nephroprotective potential to emphasis on sirtuin-1 associated machineries

Gamma oryzanol (ORZ) is a nutraceutical that is poorly water soluble with poor intestinal absorption. In the current work, ORZ was nanoformulated into uncoated and chitosan coated micelles based on methoxy-poly (ethylene glycol)-b-poly(epsilon-caprolactone) (mPEG-PCL) and poly(epsilon-caprolactone)-b-methoxy-poly(ethylene gly-col)-b-poly(epsilon-caprolactone) (PCL-PEG-PCL) copolymers for augmenting ORZ oral delivery. The physicochemical properties, morphological study, in-vitro release and safety of the nanoplaforms were determined. Importantly, the nephroprotective competence of the nanoplaforms was analyzed against acute kidney injury (AKI) rat model and the sirtuin-1 associated machineries were assessed. The results revealed that the micelles exerted particle size (PS) from 97.9 to 117.8 nm that was markedly increased after chitosan coating. The reversal of zeta potential from negative to highly positive further confirmed efficient coating. In vitro release profiles demonstrated pro-longed release pattern. The nanoforms conferred higher cell viability values than free ORZ on Vero cell line. The designed micelles displayed augmented nephroprotection compared to free ORZ with the supremacy of CS coated micelles over uncoated ones in restoring kidney parameters to normal levels. The attenuated AKI was fulfilled via the modulation of sirtuin-1 signaling pathways translated by restoring the histological features, increasing renal antioxidant states, renal autophagy and decreasing renal inflammation and renal apoptosis. These outcomes confirmed that surface modification with chitosan had a considerable leverage on micelles safety, release behavior and in vivo performance.

Automated summary

Gamma oryzanol (ORZ) was nanoformulated into uncoated and chitosan coated micelles for enhancing its oral delivery. The nanoforms displayed prolonged release pattern, higher cell viability, and augmented nephroprotection compared to free ORZ. The chitosan coated micelles showed better performance in restoring kidney parameters and modulating sirtuin-1 signaling pathways.