Thoracic interstitial injection of drug-liposomes in mice for treating atherosclerosis

Intervaginal space injection (ISI) is a novel mode of administration investigated over the last decade. After injecting nanoparticles into the intervaginal space, they can be transported along low flow resistance channels into the interstitial space. This transport has a certain delivery direction, and site-specific injection can work on specific organs or tissues. In this study, the thorax, a new ISI site in the interstitial surrounding the internal thoracic artery named the thoracic interstitial injection (tISI) was investigated. To prove the targeting ability of the tISI, two sizes of gold nanoparticles (AuNPs) (47 and 87 nm) were administered to mice. After 1 h, the biodistribution of AuNPs in the tissues was measured via single particle inductively coupled plasma mass spectrometry (spICP-MS). The results showed that the concentration of AuNPs in the aorta after tISI injection was significantly higher than that after intravenous injection. Moreover, fewer nanoparticles with larger particle sizes were observed to have entered the blood and were better targeted to the aorta. Thereafter, tanshinone IIa sodium sulfonate liposomes were administered for the treatment of aortic atherosclerosis. The proportion of aortic plaques in atherosclerotic Apoe-/- mice administered via tISI was significantly lower than that in other model animals (P < 0.001). Furthermore, the proteoglycan content and CD68-positive cell count in the plaques were significantly reduced. The vascular elastic fibers at the plaque site were thickened, and fractures were reduced. tISI was, therefore, determined to be an effective strategy for the treatment of atherosclerotic aortic plaques.