Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic ß-Cell.

ABSTRACT

Targeting current therapies to treat or prevent the loss of pancreatic islet ß-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off-target effects. Current efforts to target the ß-cell are limited by a lack of ß-cell-specific targets and the inability to test multiple targeting moieties with the same delivery vehicle. Here, we fabricate a tailorable polycaprolactone nanocapsule (NC) in which multiple different targeting peptides can be interchangeably attached for ß-cell-specific delivery. Incorporation of a cationic surfactant in the NC shell allows for the attachment of Exendin-4 and an antibody for ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) for ß-cell-specific targeting. The average NC size ranges from 250 to 300 nm with a polydispersity index under 0.2. The NCs are nontoxic, stable in media culture, and can be lyophilized and reconstituted. NCs coated with a targeting peptide were taken up by human cadaveric islet ß-cells and human stem cell-derived ß-like cells (sBC) in vitro with a high level of specificity. Furthermore, NCs successfully delivered both hydrophobic and hydrophilic cargo to human ß-cells. Additionally, Exendin-4-coated NCs were stable and targeted the mouse pancreatic islet ß-cell in vivo. Overall, our tailorable NCs have the potential to improve cell-targeted drug delivery and can be utilized as a screening platform to test the efficacy of cell-targeting peptides.