Nanoparticle-Mediated Delivery of Therapeutics for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease where excessive scar tissue develops in the lungs, causing the lungs to stiffen and lose function. This project explores a nanotechnology-based drug delivery system to improve treatment options for IPF patients by directly targeting fibrotic lung tissue. Inflammation plays a key role in IPF progression, so we investigate whether the anti-inflammatory drug, tofacitinib, could disrupt this scar tissue development. To directly deliver this drug to diseased sites, we coat them with magnetic iron oxide nanoparticles (IONPs) to form “TofaBots.” A magnetic field will guide these nanoparticles through a simulated extracellular matrix (ECM), employing mechanical and biochemical strategies to overcome IPF’s dense fibrotic barrier. Dynamic light scattering (DLS) characterizes nanoparticle size to ensure proper penetration of the ECM pores. Experiments with hydrogels will be conducted to evaluate this method’s effectiveness in navigating the ECM. Future studies will incorporate patient-derived lung tissues for more realistic testing of TofaBots. Furthermore, the nanoparticles will be coated with an enzyme, collagenase, to potentially increase the drug’s permeability through the ECM. We anticipate that collagenase-coated nanoparticles will efficiently break through the ECM, suggesting that these methods could treat IPF and potentially stop or reverse the progression of this disease.

Hello, my name is Tiffany Nguyen, and I’m a senior at George Mason University, majoring in bioengineering. I’m conducting research on Nanoparticle-Mediated Delivery of Therapeutics for Idiopathic Pulmonary Fibrosis, or IPF.
IPF is a serious lung disease in which scar tissue builds up in the lungs at an abnormal rate. This uncontrolled scarring makes the lungs stiffer and makes it difficult to breathe. The cause of IPF is unknown, which is what “idiopathic” means.
Unfortunately, there is no cure for IPF, and there are only two FDA-approved drugs to treat it (Ofev and Esbriet), both of which have limited efficacy and severe side effects. Part of the reason these drugs are not very effective is that they have difficulty penetrating the dense, stiff extracellular matrix that surrounds the sites of severe fibrosis. As a result of the degraded lung function and limited treatment options, IPF is often deadly, as it claims over 40,000 lives in the U.S. per year, which is a comparable total to breast cancer.
This research aims to address the question: “Can we improve treatment of IPF by using magnetic nanoparticles to directly deliver the drugs deep within fibrotic lung tissue?” Our approach is to attach magnetic nanoparticles to the drugs and then use magnetic fields to propel these composites through the tissue.
We call these “Tofa-Bots”, which are composites of iron oxide nanoparticles, or IONPs, and tofacitinib, an anti-inflammatory drug. If we can deliver an anti-inflammatory drug directly to the sites of severe fibrosis, we hypothesize that we can interrupt the inflammation process that is known to exacerbate fibrosis, and this could potentially slow down or even reverse the effects of this disease.
Our approach to creating Tofa-Bots involves coating tofacitinib with IONPs. This will be done by using the following procedure on the left right here. The image on the right shows a Tofa-Bot particle, where the white bumps are the IONPs that decorate the surface of the Tofa.
This semester, we have successfully measured the size distribution of these Tofa-Bots by using a tool called dynamic light scattering, in which a laser beam is passed through a sample to measure the motion and size of the particles. As a result, we saw that the size distribution was consistent, showing us that they are around 1 micrometer.
We also analyzed the Tofa-Bots by using scanning electron microscopy to confirm the attachment of the IONPs to the drug. As you can see, there are bumps on the surface of the water-dried sample, which we believe are the IONPs decorated onto the surface of the tofacitinib.
We have also done some preliminary testing of the IONPs in different hydrogel concentrations as a model of fibrotic lung tissue. As a result, I observed that the nanoparticles move more efficiently in lower hydrogel concentrations, showing us that the Tofa-Bots successfully penetrated the hydrogels. In addition, I also designed a 3D-printed magnet holder, ensuring that the magnet stays in place during these experiments.
Our next step is to test the Tofa-Bots in hydrogels, allowing us to see how well this method works. In the future, we also plan to incorporate patient-derived lung tissues in these hydrogels for even more realistic testing. To further enhance the efficiency of Tofa-Bots, we plan to use collagenase as an additional layer. Collagenase is an enzyme that breaks down collagen, which is one of the main components of the ECM. We believe that the use of collagenase may help these nanoparticles move more efficiently.
I would like to show appreciation to my mentor, Dr. Moran, for supporting me and guiding me throughout this project, as well as Dr. Singh for providing additional guidance. I would also like to thank Dr. Grant and her team for developing the hydrogels to help with our research, along with the INOVA hospital and IPF patients for donating their lung tissue. Lastly, I would like to thank the OSCAR and URSP programs for providing me with the funding and information I need to work on this project. Thank you!