A Novel Hybrid Drug Delivery System for Treatment of Aortic Aneurysms

Int J Mol Sci. 2020 Aug 2;21(15):5538. doi: 10.3390/ijms21155538.

Abstract

Ongoing aortic wall degeneration and subsequent aneurysm exclusion failure are major concerns after an endovascular aneurysm repair with a stent-graft. An ideal solution would be a drug therapy that targets the aortic wall and inhibits wall degeneration. Here, we described a novel drug delivery system, which allowed repetitively charging a graft with therapeutic drugs and releasing them to the aortic wall in vivo. The system was composed of a targeted graft, which was labeled with a small target molecule, and the target-recognizing nanocarrier, which contained suitable drugs. We developed the targeted graft by decorating a biotinylated polyester graft with neutravidin. We created the target-recognizing nanocarrier by conjugating drug-containing liposomes with biotinylated bio-nanocapsules. We successfully demonstrated that the target-recognizing nanocarriers could bind to the targeted graft, both in vitro and in blood vessels of live mice. Moreover, the drug released from our drug delivery system reduced the expression of matrix metalloproteinase-9 in mouse aortas. Thus, this hybrid system represents a first step toward an adjuvant therapy that might improve the long-term outcome of endovascular aneurysm repair.

Keywords: aortic aneurysm; bio-nanocapsule; drug delivery system; endovascular aneurysm repair.

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Aneurysm / therapy*
  • Avidin / chemistry
  • Blood Vessel Prosthesis*
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Nanostructures / chemistry
  • Prosthesis Design
  • Quinolines / administration & dosage*
  • Quinolines / chemistry
  • Treatment Outcome

Substances

  • Drug Carriers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • neutravidin
  • Avidin
  • Matrix Metalloproteinase 9
  • pitavastatin