Targeted Drug Delivery to the Pulmonary Endothelium Using Liposomal Nanocarriers and Red Blood Cell Super Carriers

ABSTRACT

Myriad compounds have desirable effects on specific cell subtypes but cannot be used as medications because of toxic effects on surrounding cells or organs. While nanomedicine, in particular targeted nanomedicine, has improved organ-level targeting, delivery of drug to a specific cell type remains challenging. We have previously demonstrated that red blood cells (RBC) can be used to as super-carriers that boost delivery of dual-targeted liposomes to the pulmonary endothelium such that up to 65% of the total dose is delivered to the lungs. In contrast, freely injected single-targeted liposomes deliver, at best, 25% of total dose to the lungs. These precisely designed liposomal drug carriers are coated with antibodies to both their RBC carriers and the destination target cell. We IV injected RBC-loaded dual-targeted liposomes into a murine model, allowed them to circulate for 30 minutes, then used flow cytometry to quantify liposome binding to endothelial cells and leukocytes. We found that, in addition to a > 2.5-fold increase in delivery to the lungs compared to freely injected single-targeted liposomes, there was an additional > 6-fold increase in delivery to the endothelial cell subpopulation. Specifically, the percent of endothelial cell population bound by liposomes increased from 4% to 85% using dual-targeted RBC-bound liposomes. This corresponds to an overall 55-fold increase in drug delivered to the pulmonary endothelium. As lipid-based nanocarriers such as those used in several cancer therapeutics and those used in Covid vaccines grow in popularity, targeting to specific cell populations will become increasingly important.