Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination

Abstract

Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We have generated a novel library of vectors derived from poly(β-amino ester)s (PBAEs) including oligopeptide-termini and a natural ligand, mannose, for targeted transfection of antigen presenting cells (APCs) such as Langerhans cells and macrophages in the dermal milieu. Our results reaffirmed terminal decoration of PBAEs with oligopeptide chains as a powerful tool to induce cell-specific transfection, identifying an outstanding candidate with a ten-fold increased transfection efficiency over commercial controls in vitro. The inclusion of mannose in the PBAE backbone rendered an additive effect and increased transfection levels, achieving superior gene expression in human monocyte-derived dendritic cells and other accessory antigen presenting cells. Moreover, top performing candidates were capable of mediating surface gene transfer when deposited as polyelectrolyte films onto transdermal devices such as microneedles, offering alternatives to conventional hypodermic administration. We predict that the use of highly efficient delivery vectors derived from PBAEs could advance clinical translation of nucleic acid vaccination over protein- and peptide-based strategies.

Antibacterial cationic polymers: A novel approach for combating bacterial infections

“…Because of their ease of synthesis, low cost, and outstanding biocompatibility, PBAEs have received a lot of attention in recent years. PBAEs containing oligopeptide chains have been identified as a strong tool for inducing cell-specific transfection, with a ten-fold improvement in transfection effectiveness over commercial controls in vitro [22]. Various Poly(-amino ester)s (PAE) derivatives of polytrimethylenimines exhibit effective antibacterial activity against clinical isolates resistant to conventional antibiotics.…”