Mathematical modeling of shear-activated targeted nanoparticle drug delivery for the treatment of aortic diseases

Biomech Model Mechanobiol. 2022 Feb;21(1):221-230. doi: 10.1007/s10237-021-01530-9. Epub 2021 Nov 8.

Abstract

The human aorta is a high-risk area for vascular diseases, which are commonly restored by thoracic endovascular aortic repair. In this paper, we report a promising shear-activated targeted nanoparticle drug delivery strategy to assist in the treatment of coarctation of the aorta and aortic aneurysm. Idealized three-dimensional geometric models of coarctation of the aorta and aortic aneurysm are designed, respectively. The unique hemodynamic environment of the diseased aorta is used to improve nanoparticle drug delivery. Micro-carriers with nanoparticle drugs would be targeting activated to release nanoparticle drugs by local abnormal shear stress rate (SSR). Coarctation of the aorta provides a high SSR hemodynamic environment, while the aortic aneurysm is exposed to low SSR. We propose a method to calculate the SSR thresholds for the diseased aorta. Results show that the upstream near-wall area of the diseased location is an ideal injection location for the micro-carriers, which could be activated by the abnormal SSR. Released nanoparticle drugs would be successfully targeted delivered to the aortic diseased wall. Besides, the high diffusivity of the micro-carriers and nanoparticle drugs has a significant impact on the surface drug concentrations of the diseased aortic walls, especially for aortic aneurysms. This study preliminary demonstrates the feasibility of shear-activated targeted nanoparticle drug delivery in the treatment of aortic diseases and provides a theoretical basis for developing the drug delivery system and novel therapy.

Keywords: Aortic aneurysm; Coarctation of the aorta; Computational fluid dynamics; Hemodynamics; Nanoparticles.

MeSH terms

  • Aorta, Thoracic
  • Aortic Aneurysm*
  • Aortic Coarctation*
  • Drug Delivery Systems
  • Hemodynamics
  • Humans
  • Models, Cardiovascular
  • Nanoparticles*
  • Stress, Mechanical