Title : Self-assembly of nobiletin into nanoparticles for improved therapeutic potential
Abstract:
Nobiletin, a biologically active polymethoxyflavone derived from citrus peel has attracted considerable attention due to its demonstrated antioxidant, anti-inflammatory and anticancer properties. However, its clinical translation remains significantly restricted by two major limitations: low aqueous solubility and poor oral bioavailability. To address these limitations, this study investigates a carrier-free strategy in which nobiletin molecules themselves form nanoscale assemblies, which enables a self -assembled nanoparticle formulation. Using molecular dynamics simulations, the molecular mechanism governing the spontaneous clustering and aggregation of nobiletin in aqueous media is explored. It is clear from the study that nobiletin molecules undergo rapid nucleation, followed bygrowth into stable nanoaggregates driven by intermolecular hydrogen bonding, hydrophobic interactions and π-π stacking between aromatic rings. Structural stability was evaluated through RMSD, radius of gyration, and binding energy analysis, confirming that the nanoparticle configuration is energetically favourable. Visualisation and cluster size evolution further support the aggregation of nobiletin nanoparticle formation. This carrier-free nano self-assembly approach offers a promising pathway to increase the aqueous solubility and potential bioavailability of nobiletin. The findings provide a mechanistic foundation for future experimental validation, including nano-formulation synthesis and cellular uptake studies. Overall, this MD-driven design strategy positions nobiletin nanoparticles as a viable therapeutic delivery concept and aligns with minimal excipients drug delivery.
