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Published on: September 18, 2015
Magnetically responsive PLGA-magnetite nanoparticles for in vitro stent targeting and delivery of therapeutic agents
Michael Kitching1, Dorota Kozlowska1, Roa Bashmail1
1School of Biotechnology, Dublin City University, Co. Dublin, Ireland.
Insights
Researchers developed magnetic nanoparticles for drug delivery to stents, aiming to prevent restenosis. These nanoparticles can be reloaded with medication, offering a new approach to treating coronary artery disease.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Nanotechnology
Background:
- Coronary artery disease (CAD) involves vessel obstruction, often treated with stents.
- In-stent restenosis, caused by smooth muscle cell proliferation, limits stent efficacy.
- Current drug-eluting stents (DES) have fixed drug loads and cannot be replenished.
Purpose of the Study:
- To develop a magnetically responsive nanoparticle platform for targeted drug reloading in stents.
- To engineer poly (lactic-co-glycolic acid) magnetite nanoparticles (PLGA-MNPs) for drug delivery.
- To evaluate the efficacy of drug-loaded PLGA-MNPs in vitro.
Main Methods:
- PLGA-MNPs were engineered to encapsulate paclitaxel or γ-secretase inhibitors.
- Nanoparticle characterization included dynamic light scattering and electron microscopy.
- In vitro studies assessed nanoparticle binding to stents, drug release, and cellular responses under magnetic fields.
Main Results:
- PLGA-MNPs demonstrated stable suspension properties and magnetic field-enhanced retention on stents.
- Paclitaxel-loaded nanoparticles inhibited stem cell proliferation, with increased efficacy under magnetic fields.
- γ-secretase inhibitor-loaded nanoparticles reduced Notch-responsive gene expression, and magnetic fields influenced drug release and gene expression.
Conclusions:
- Magnetically responsive PLGA-MNPs show feasibility as a stent-targeted drug delivery platform.
- This approach offers potential for replenishing drug levels after stent implantation.
- Further in vivo studies are needed to confirm safety and therapeutic efficacy.
Abstract:
Coronary artery disease presents as an obstruction to coronary blood flow due to the presence of a vascular lesion. Treatment options include percutaneous transluminal coronary angioplasty and the deployment of a vascular stent to keep the artery open. However, in-stent restenosis can still occur because of neointimal hyperplasia driven by the accumulation of vascular smooth muscle cell (VSMC)-like cells within the stented vessel segment. Drug-eluting stents (DES) reduce restenosis by locally releasing anti-proliferative agents. Yet, current DES platforms are limited by fixed drug loading at implantation and the inability to replenish the drug at the stent after depletion. Here, we developed a magnetically responsive nanoparticle platform as a proof-of-concept strategy for targeted stent drug reloading. Poly (lactic-co-glycolic acid) magnetite nanoparticles (PLGA-MNPs) were engineered to encapsulate paclitaxel or the γ-secretase inhibitors, DAPT and Compound E. Nanoparticles were characterised by dynamic light scattering, electron microscopy, and inductively coupled plasma atomic emission spectroscopy. Their ability to bind stainless steel stents, release drugs, and modulate cellular responses was examined in vitro. PLGA-MNPs exhibited a mean hydrodynamic diameter of ∼215 nm with low polydispersity and stable suspension properties. Fluorescence imaging demonstrated increased retention of FITC-labelled PLGA-MNPs on stainless steel stents in the presence of a static magnetic field. Paclitaxel-loaded PLGA-MNPs inhibited murine mesenchymal stem cell proliferation, with enhanced efficacy observed under magnetic field exposure. Similarly, γ-secretase inhibitor-loaded PLGA-MNPs attenuated Jagged-1-induced expression of myogenic and Notch-responsive genes in vitro. Drug release from PLGA-MNPs was increased in the presence of a magnetic field over extended incubation periods. Notably, exposure to a static magnetic field alone also influenced gene expression, indicating that magnetic field effects must be considered when interpreting biological outcomes. Collectively, these findings demonstrate the feasibility of magnetically responsive PLGA-MNPs as a stent-targeted drug delivery platform. Further studies under physiological flow conditions and in vivo vascular injury models will be required to establish safety, targeting efficiency, and therapeutic efficacy.
