Advancing Manufacturing Methods for Drug Delivery Carriers for the Treatment of Lymph Node Resident Diseases

• Ryann Chatfield, Biomedical Engineering, University of Delaware

• Jason Gleghorn, Biomedical Engineering, University of Delaware

One of the main challenges faced when trying to treat metastatic cancer is that disease is able to persist in locations such as the lymph node (LN) where many small molecule drugs display poor penetration into the LN lobule. Subsequently, cancer cells that persist in the lobule can spread into other vital organs due to lack of therapeutic levels of chemotherapeutic drugs, as they are separated from the blood by tight endothelial barriers. Therefore, there is an urgent need for a drug delivery vehicle that allows for targeted delivery of anti-cancer drugs into the LN lobule. In recent years, new delivery systems have been developed to improve drug transport into the lymph nodes, including nanoparticle and cell-derived systems; however, these still have limitations such as rapid clearance, off-target toxicity, and only local routes of administration. Our lab has leveraged the ways cells move through the body, to develop a cell-mimetic delivery vehicle capable of moving through the blood and targeting the lymph node. Currently, we are focused on producing and characterizing cell-mimetic membrane-wrapped microparticles.  The microparticles use a “trojan horse” strategy by mimicking a lymphocyte’s physical and surface functional characteristics to deliver small-molecule chemotherapeutics to the LN. We have developed a strategy to isolate Jurkat cell membranes and wrap them around a polystyrene core to fabricate a cell-mimetic microparticle. Our isolation protocol results in high-purity membrane isolates, which retain key membrane proteins. SEM imaging and immunolabeling post-wrapping have revealed that polystyrene beads are successfully within cell-derived membranes and a key membrane-targeting protein, L-selectin, is present. Future works will look toward optimizing production yields, wrapping drug-laden hydrogel cores, and testing membrane-wrapped microparticle uptake in vivo. The continued refinement of this cell-mimetic microparticle manufacturing holds promise for improved drug delivery to the lymph nodes and metastatic cancer.