Delivery of Cinnamic Aldehyde Antioxidant Response Activating nanoParticles (ARAPas) for Vascular Applications

Abstract

Selective delivery of nuclear factor erythroid 2-related factor 2 (Nrf2) activators to the injured vasculature at the time of vascular surgical intervention has the potential to attenuate oxidative stress and decrease vascular smooth muscle cell (VSMC) hyperproliferation and migration towards the inner vessel wall. To this end, we developed a nanoformulation of cinnamic aldehyde (CA), termed Antioxidant Response Activating nanoParticles (ARAPas), that can be readily loaded into macrophages ex vivo. The CA-ARAPas-macrophage system was used to study the effects of CA on VSMC in culture. CA was encapsulated into a pluronic micelle that was readily loaded into both murine and human macrophages. CA-ARAPas inhibits VSMC proliferation and migration, and activates Nrf2. Macrophage-mediated transfer of CA-ARAPas to VSMC is evident after 12 h, and Nrf2 activation is apparent after 24 h. This is the first report, to the best of our knowledge, of CA encapsulation in pluronic micelles for macrophage-mediated delivery studies. The results of this study highlight the feasibility of CA encapsulation and subsequent macrophage uptake for delivery of cargo into other pertinent cells, such as VSMC.

Biological fate, functional properties, and design strategies for oral delivery systems for cinnamaldehyde

“…71 Cartaya et al encapsulated CA into poly(lactic- co -glycolic acid)-poly(siloxane) pluronic micelles using a direct dissolution method to prepare antioxidant response-activated nanospheres, providing complete drug integrity protection and selective targeting of cells, effectively inhibiting the proliferation and migration of vascular smooth muscle cells. 72 CA-loaded micelles significantly increased the content of GSH compared to free unformulated CA. Raffai et al reported that CA-loaded micelles were synthesized by the Michael addition reaction.…”

Unleashing the Potential of Nrf2: A Novel Therapeutic Target for Pulmonary Vascular Remodeling

“…The expression of Nrf2 in rodent models of primary or secondary PH is decreased [130]. The selective delivery of Nrf2 activators to the injured vasculature has the potential to attenuate oxidative stress and decrease VSMC hyper-proliferation and migration towards the inner vessel wall [131]. Nrf2 gene transfer or Nrf2-inducing drugs such as sulforaphane, epigallocatechin gallate, cinnamic aldehyde, and exendin-4 have shown therapeutic applications in vascular diseases [132][133][134][135][136].…”

The Mechanism of Nrf2/ARE Signaling Pathway in Periodontitis with Atherosclerosis

“…The migration and proliferation of smooth muscle cells in arterial media is an important link in the progression of atherosclerosis. During vascular surgical intervention, selective delivery of Nrf2 activator to injured blood vessels can reduce oxidative stress, reduce excessive proliferation of vascular smooth muscle cells (VSMC) and migration to the inner wall of blood vessels [30]. The proliferation and migration of smooth muscle cells undergo phenotypic transfer and become a synthetic type, which is conducive to lipid absorption and myogenic foam cells formation.…”