Control of low-density lipoprotein concentration in the arterial wall by proportional drug-encapsulated nanoparticles

IEEE Trans Nanobioscience. 2012 Dec;11(4):394-401. doi: 10.1109/TNB.2012.2217382. Epub 2012 Sep 19.

Abstract

Atherosclerosis, or hardening of the arteries, is one of the major causes of death in humans. High accumulation of Low-Density Lipoprotein (LDL) macromolecules within the arterial wall plays a critical role in initiation and development of atherosclerotic plaques. This paper proposes a proportional drug-encapsulated nanoparticle (PDENP) that utilizes a simple piecewise-proportional controller to realize swarm feedback control of LDL concentration in the interior of the arterial wall. In contrast to the competing strategies on nanorobotics, PDENPs carry simpler hardware architecture in order to be more reasonably realized technologically as well as to penetrate the interior arterial wall. Furthermore, in contrast to the existing targeted DENPs that usually target the surface proteins of atherosclerotic plaque, the proposed PDENPs directly sense the LDL level in the arterial walls. Hence, they can diagnose abnormal LDL accumulation before plaque formation, prevent critical growth of atherosclerotic plaques, while considerably reducing the unwanted drug side effects in healthy tissue. Simulation results on a well-known mathematical model of the arterial wall demonstrate that the proposed approach successfully reduces the LDL level to a desired value in the arterial wall of a patient with very high LDL level. Also, the mass of the released drug by PDENPs in a healthy wall is 11 times less than its corresponding value in an unhealthy wall.

MeSH terms

  • Arteries / metabolism*
  • Computer Simulation
  • Endothelium, Vascular / metabolism*
  • Humans
  • Lipoproteins, LDL / analysis
  • Lipoproteins, LDL / metabolism*
  • Models, Cardiovascular*
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / chemistry
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / prevention & control*
  • Silicon Dioxide / administration & dosage
  • Silicon Dioxide / chemistry

Substances

  • Lipoproteins, LDL
  • Pharmaceutical Preparations
  • Silicon Dioxide