Liposomal codelivery of inflammation inhibitor and collagen protector to the plaque for effective anti-atherosclerosis

Plaque plays a central role in atherosclerosis (AS) progression, whereas inflammation and destruction of the plaque microenvironment contribute to plaque advancement. As a result, a therapy regime, which combines anti-inflammation and inhibition-degradation of plaque matrix, appears to be a promising strat-egy to combat AS. Herein, we report a pH-sensitive liposome co-loading with the anti-inflammatory agent (oridonin, ORD) and plaque-collagen protector (marimastat) for anti-AS therapy. ORD was first conjugated with hyaluronic acid (HA) to target the inflammation contributor, pro-inflammatory macrophages. Then, the conjugate assembled onto the MATT-loaded liposomes. The co-loaded system ( similar to 150 nm) significantly improved pharmacokinetics over the liposomes without anchoring the conjugate and accumulated effec-tively in the plaque. The preparation administration allowed efficient anti-AS activities in high-fat diet (HFD)-Apoe -/- mice by decreasing the pro-inflammatory cytokine expression in the serum, lessening the lesion area, alleviating the plaque collagen degradation, promoting macrophage polarization from pheno-typic M1 to M2, reducing T helper (Th) 17 cells (Th17)/T regulatory cells (Tregs) and Th1/Th2 ratio, etc. Furthermore, the serum determination in AS patients demonstrated high expression of the inflammatory cytokines, indicating our finding may offer a potential guideline for clinical practice.(c) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

In this study, a pH-sensitive liposome co-loaded with an anti-inflammatory agent and a plaque-collagen protector was developed for the treatment of atherosclerosis. The co-loaded system showed improved pharmacokinetics and effective accumulation in plaque, leading to efficient anti-atherosclerosis activities. The findings provide a potential guideline for clinical practice.