Delivery of Polymeric Nanoparticles to Target Vascular Diseases

Abstract

Current advances in nanotechnology have paved the way for the early detection, prevention and treatment of various diseases such as vascular disorders and cancer. These advances have provided novel approaches or modalities of incorporating or adsorbing therapeutic, biosensor and targeting agents into/on nanoparticles. With significant progress, nanomedicine for vascular therapy has shown significant advantages over traditional medicine because of its ability to selectively target the disease site and reduce adverse side effects. Targeted delivery of nanoparticles to vascular endothelial cells or the vascular wall provides an effective and more efficient way for early detection and/or treatment of vascular diseases such as atherosclerosis, thrombosis and Cerebrovascular Amyloid Angiopathy (CAA). Clinical applications of biocompatible and biodegradable polymers in areas such as vascular graft, implantable drug delivery, stent devices and tissue engineering scaffolds have advanced the candidature of polymers as potential nano-carriers for vascular-targeted delivery of diagnostic agents and drugs. This review focuses on the basic aspects of the vasculature and its associated diseases and relates them to polymeric nanoparticle-based strategies for targeting therapeutic agents to diseased vascular site.

Keywords: Atherosclerosis; Nanomedicine; Polymeric nanoparticles; Targeted delivery; Thrombosis; Vascular disease.

Figure 1

Confocal images exhibiting polymeric nanoparticles distribution or penetration in vessel wall of aorta abdominalis of New Zealand white rabbits. Polymeric nanoparticles are labeled yellow-green, (A) Control, (B) 514-nm polymeric nanoparticles accumulation on the luminal surface, (C) Distribution of 217-nm polymeric nanoparticles in the inner media section, and (D) Distribution of 217-nm polymeric nanoparticles in adventitial region of vessel wall. L = lumen region, M = media section of the vessel, and A = adventitia section of the vessel. (Reprinted with permission ⁸³).

Figure 2

Confocal images showing distribution of 110-nm polymeric particles in: (A) a non-atherosclerotic vessel segment, and (B) in comparison to an atherosclerotic segment. L = lumen region of the vessel, P = atherosclerotic plaque. (Adapted with permission ⁸³).

Figure 3

(A) sLe^A-spheres binding in pulsatile reconstituted blood flow (open bar = profile I at peak WSR = 1000 s⁻¹ and shaded bar = profile II). (B) Ratio of sLe^A-spheres adhesion in pulsatile flow to adhesion in laminar flow at peak shear rates (1000 s⁻¹ for profile I and 1200 s⁻¹for profile II) (Adapted with permission²).

Figure 4

Images showing particles bound at the inner wall of mouse lumen. Images (A) and (B) show2 µm particles while images (C) and (D) represent 0.5 µm particles bound at the inner wall of mouse lumen. (A and C) fluorescent and (B and D) brightfield images of H&E stained images. (Adapted with permission²).

Figure 5

Kinase-insert domain receptor (KDR) immunofluorescence staining of pig aorta endothelial cells (PAE) or KDR-PAE cells grown on untreated poly L-lactic acid (PLLA) or surface-modified PLLA film. (a) PAE grown on untreated PLLA, (b) PAE grown on PLLAPVAA-(EDC)-FN-VEGF, (c) KDR-PAE grown on untreated PLLA, and (d) KDR-PAE grown on PLLAPVAA-(EDC)-FN-VEGF. (PVAA= poly(vinylacetic acid, EDC) = ethyl(dimethylaminopropyl) carbodiimide, FN = fibronection, VEGF = vascular endothelial growth factor). (Adapted with permission¹¹⁸)