Development of a Manufacturing Pipeline For Cell-Mimetic Drug Carriers

• Aaron Maniyatte, Biomedical Engineering, University of Delaware

• Jason Gleghorn, Biomedical Engineering, University of Delaware

Poor drug penetration in the lymph node (LN) is one of the biggest challenges in treating LN resident metastatic cancer. Current clinical treatments involve the use of high systemic doses of small molecule therapeutics that fail to penetrate into the LN and cause off-target toxicities throughout the body. There are some alternative strategies currently being investigated, such as engineered nanoparticles, but they still have certain limitations. Nanoparticles do successfully increase circulation of the drug within the bloodstream, but the majority of the carriers get cleared by body’s native defense mechanism, thereby reducing the chances of delivering the drug to the LN at a therapeutic levels (1). A solution our lab has been investigating to improve drug penetration to the LN is to use cell-mimetic microparticles (MPs). This work is focused on optimizing membrane isolation and wrapping capabilities. We developed cell membrane isolation methods for efficient and intact membrane recovery. Subsequently, we optimized methods to wrap membranes around polystyrene (PS) MPs as a test core.  We verified successful wrapping of MPs via confocal microscopy and further confirmed the presence of membrane on the MP surface using scanning electron microscopy (SEM). Additionally we quantified the wrapping efficiency using flow cytometry and quantified the amount of lipid wrapped on a single particle using phospholipid quantification technique. Moving forward we will test the targeting capability of the membrane of these carriers in vitro.

1. Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, Dvorak HF and Chan WCW, Nat. Rev. Mater, 2016, 1, 1–12.