Hydroxypropyl-β-cyclodextrin/Oridonin and Trehalose loaded nanovesicles attenuate foam cells formation and regulate the inflammation

• Multi-loaded nanovesicles systems were established to encapsulate both hydrophilic and hydrophobic drugs. • This Multi-loaded H9-HePC NVs effectively reduced lipid over-accumulation in foam cells, regulated the release of inflammatory cytokines, and there had a synergistic effect on the inhibition of cell lipid over-accumulation. Hydroxypropyl-β-Cyclodextrin (HP-β-CD) was used to form the HP-β-CD/Oridonin inclusion complex. Then, the novel Multi-loaded nanovesicles systems (NVs) were established to encapsulate both hydrophilic (Trehalose) and hydrophobic drugs (Oridonin inclusion complex) with peptides. NVs had an average size of 224.4 ± 10.84 nm and a zeta potential of 17.83 ± 1.05 mV. Furthermore, these NVs significantly decreased lipid over-accumulation, and reverse the formation of foam cells in RAW264.7 cells. Oridonin and Trehalose in NVs provided significant synergistic effects to inhibit lipid over-accumulation (CI < 1). In addition, NVs could modulate the release of IL-1β, IL-6 and TNF-α, promote the formation of autophagosomes. Taken together, the Multi-loaded NVs may be used as an effective drug delivery system, providing new insights into decrease the formation of foam cells and regulate the inflammation.