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.
Highlights
Sodium bicarbonate (NaHCO3 ) reacts with protons in an acidic environment to produce salt and carbonic acid, which in turn can be broken down into CO2 and water [25]. Based on these chemical properties of PLGA and NaHCO3 and to enhance the drug targeting of PTX, we constructed a pH-responsive nanomaterial comprising PLGA nanoparticles loaded with PTX and NaHCO3 as a pH-sensitive therapeutic agent (PTX-NaHCO3 PLGA NPs) to accelerate drug release in an acidic microenvironment
We believe that the -COOH group will not lead to acidic hydrolysis of PTX-NaHCO3 -PLGA NPs (Figure 1D)
As observed in the hematoxylin and eosin (H&E) sections, the area of the intima was reduced in the free PTX and NaHCO3-PLGA NPs treatment groups compared with the model group, but no statistical difference was observed between them, as shown by quantitative analysis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Sodium bicarbonate (NaHCO3 ) reacts with protons in an acidic environment to produce salt and carbonic acid, which in turn can be broken down into CO2 and water [25] Based on these chemical properties of PLGA and NaHCO3 and to enhance the drug targeting of PTX, we constructed a pH-responsive nanomaterial comprising PLGA nanoparticles loaded with PTX and NaHCO3 as a pH-sensitive therapeutic agent (PTX-NaHCO3 PLGA NPs) to accelerate drug release in an acidic microenvironment. We evaluated the therapeutic efficacy and biocompatibility of the PTX-NAHCO3 -PLGA NPs in the animal model These results highlight the potential of pH-responsive nanomaterials as a good drug delivery platform to target the injury site and to release drugs to treat revascularization. Design of pH-responsive nanoparticles for the treatment of vascular restenosis
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