Tanshinone IIA-Loaded Micelles Functionalized with Rosmarinic Acid: A Novel Synergistic Anti-Inflammatory Strategy for Treatment of Atherosclerosis

• Published in: Journal of pharmaceutical sciences 2022-10, Vol.111 (10), p.2827-2838
• Main Authors: Liu, Meixuan, Liu, Sha, Zhu, Xiaosu, Sun, Yiying, Su, Linyu, Yu, Hairong, Liu, Deshuai, Li, Ying, Du, Yuan, Liu, Rongxia, Sun, Kaoxiang
• Format: Article
• Language: English
• Subjects: Abietanes; Amides; Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Cinnamates; Depsides; Endothelial Cells - metabolism; Lipopolysaccharides; Mice; Micelles; NF-kappa B - metabolism; Polyethylene Glycols - chemistry; Polymers; Reactive Oxygen Species - metabolism; Rosmarinic Acid; synergistic; tanshinone IIA; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2022.05.007

Rosmarinic acid (RA) and tanshinone IIA (TA) which are effective components in Salvia miltiorrhiza show anti-inflammatory potential against atherosclerosis. Based on polysulfated propylene-polyethylene glycol (PPS-PEG), RA was grafted onto this polymer via amide bonds to form a micelle carrier for TA encapsulation: PPS-PEG-RA@TA. A potent inhibitory effect on lipopolysaccharide (LPS) -induced proliferation of endothelial cells with significant intracellular uptake was observed with this system. This could have been the result of release of TA in a reactive oxygen species (ROS) environment and stronger antioxidant effect of RA. The synergistic effect was optimized when the combination was used in a molar ratio of 1:1. Mechanistic studies showed that, compared with PPS-PEG-RA and TA+RA, PPS-PEG-RA@TA micelles could more effectively regulate the nuclear factor-kappa B (NF-κB) pathway to reduce expression of vascular cell adhesion molecule-1 (VCAM-1), inhibit the inflammatory cascade and reduce endothelial-cell injury. One month after intravenous injection of PPS-PEG-RA@TA micelles, the plaque area in murine aortic vessels was reduced significantly, and serious toxic side-effects were not observed in vivo, along with excellent biocompatibility. In summary, PPS-PEG-RA@TA micelles could achieve synergistic treatment of atherosclerosis. [Display omitted]