Amalgamation of postbiotic, polysaccharide and plant flavonoid in nanostructured lipid carrier for treatment of rotenone-induced Parkinson's disease

A novel, multifunctional nanostructured lipid carrier (NLC) formulation has been developed by amalgamating a plant flavonoid, Xanthohumol (XHM), with postbiotic sodium butyrate (SB), and natural polysaccharides guar gum (GG) and pectin (PEC) to deliver multiple benefits of controlled release, gut microbiota modulation and neuroprotection. The optimized liquid NLC (L-XHM-NLC) was developed using Box-Behnken Design, followed by its solidification into solid NLC (SXHM-NLC) using SB and polysaccharides as both stabilizers and nutraceuticals. The final formulation demonstrated particle size of 112.0 nm, zeta potential of −10.6 mV, and entrapment efficiency EE of 98.7 %. In vitro release studies revealed 2.66-fold and 1.48-fold enhancement in the release of XHM from S-XHM-NLC as compared to naïve XHM and L-XHM-NLCs. The significant (P < 0.05) enhancement in Cmax and AUC was observed in the case of both S-XHM-NLC, with SB and without SB, indicating enhancement in absorption and oral bioavailability of XHM from NLCs as compared to naïve XHM. S-XHM-NLC with SB exhibited a 5.3-fold enhancement in AUC and a 4.7-fold enhancement in Cmax when compared to naïve XHM. Pharmacodynamic evaluations in the rotenone-induced PD model in rats showed that S-XHM-NLC with SB significantly improved motor coordination, grip strength, and sensory-motor function. Biochemical analyses revealed a 3.2-fold increase in dopamine levels, along with the marked elevation in antioxidant enzymes and reduction in oxidative stress markers. ELISA and Western blot analyses confirmed downregulation of pro-inflammatory cytokines and upregulation of tyrosine hydroxylase enzyme activity. Histopathological assessment corroborated the neuroprotective potential of the formulation by showing preserved neuronal integrity in the substantia nigra.