pH-Responsive Nanoparticles for Delivery of Paclitaxel to the Injury Site for Inhibiting Vascular Restenosis

Abstract

A high incidence of restenosis has been reported at the site of inflammation following angioplasty and stent implantation. The anti-proliferative drug paclitaxel (PTX) could help to reduce inflammation and restenosis; however, it has poor water solubility and serious adverse side effects at high doses. Given the presence of metabolic acidosis at the site of inflammation, we hypothesized that nanoparticles that are responsive to low pH could precisely release the loaded drug at the target site. We successfully constructed pH-responsive poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PTX and NaHCO3 as a pH-sensitive therapeutic agent (PTX-NaHCO3-PLGA NPs). The NPs exhibited remarkable pH sensitivity and a good safety profile both in vitro in rat vascular smooth muscle cells and in vivo in Sprague Dawley rats after tail vein injection. In the rat model, the PTX-NaHCO3-PLGA NPs treatment group showed suppressed intimal proliferation following balloon-induced carotid artery injury compared with that of the saline-treated control. Overall, these results demonstrate that our newly developed pH-responsive nanodrug delivery platform has the potential to effectively inhibit restenosis.

Chitosan-salvianolic acid B coating on the surface of nickel-titanium alloy inhibits proliferation of smooth muscle cells and promote endothelialization

“…Placement of the stent within the blood vessel leads to biocompatibility issues caused by its foreign body properties (Zhu et al, 2022). To tackle this issue, experiments related to blood compatibility were conducted.…”

Targeted Nanoparticles for the Binding of Injured Vascular Endothelium after Percutaneous Coronary Intervention

“…PLGA NPs, approved by the US FDA, have been extensively developed and used as drug delivery vehicle and diagnostics in CVDs [ 47 , 48 ]. For instance, the delivery of NPs loaded with anti-proliferative agent after percutaneous transluminal coronary angioplasty or balloon angioplasty to treat restenosis [ 49 , 50 , 51 ]. Moreover, due to its ease of surface conjugation with the chemical reactions, the PLGA NPs are a suitable candidate for anchoring HuscFv with controlled conjugation orientation [ 52 ].…”

“…Our fabricated material is considered as submicron material with sizes ranging from 100 nm–1 µm [ 60 ]. However, according to several nanomaterial studies, they also reported polymeric NPs with sizes larger than 100 nm [ 49 , 52 ]. Therefore, the polymeric particles in the present study were represented as NPs.…”

Less Is More: Developments in Nanotechnology for Antirestenosis Therapies

“…Another group designed PLGA nanoparticles functionalized with encapsulated sodium bicarbonate to selectively release paclitaxel following particle disintegration triggered by low pH associated with metabolic acidosis at the site of atherosclerotic inflammation. 119 Polyurethanes are similarly readily degradable and have been used in several formulations to produce redox-responsive nanoparticles that target aortic endothelium and atherosclerotic plaque. These polyurethane-based particles have been used in ligand-receptor targeting strategies using glycoprotein and anti-CD34 antibodies to locally outcompete platelet aggregation on injured endothelium and capture circulating endothelial progenitor cells to limit inflammation and promote in situ vessel repair.…”