Design and Characterization of Lipid Nanocarriers for Oral Delivery of Immunotherapeutic Peptides

Abstract

The use of therapeutic proteins and peptides is of great interest for the treatment of many diseases, and advances in nanotechnology offer a path toward their stable delivery via preferred routes of administration. In this study, we sought to design and formulate a nanostructured lipid carrier (NLC) containing a nominal antigen (insulin peptide) for oral delivery. We utilized the design of experiments (DOE) statistical method to determine the dependencies of formulation variables on physicochemical particle characteristics including particle size, polydispersity (PDI), melting point, and latent heat of melting. The particles were determined to be non-toxic in vitro, readily taken up by primary immune cells, and found to accumulate in regional lymph nodes following oral administration. We believe that this platform technology could be broadly useful for the treatment of autoimmune diseases by supporting the development of oral delivery-based antigen specific immunotherapies. Highlights3-5 bullets, 85 char or less O_LIA Design of Experiments method led the formulation of biocompatible nanoparticles C_LIO_LINLC accumulate into gut-draining lymphatic tissues following oral administration C_LIO_LINLC protect their antigen cargo and promote its presentation C_LIO_LINLC formulation is well-suited for oral delivery of immunomodulatory agents C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/478027v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1d18054org.highwire.dtl.DTLVardef@14038ddorg.highwire.dtl.DTLVardef@1555abdorg.highwire.dtl.DTLVardef@b83a42_HPS_FORMAT_FIGEXP M_FIG The development of nanostructured lipid carriers containing a nominal antigen (insulin peptide) for oral delivery consists on (1) nanoparticle formulation using a statistical method, (2) in-vitro studies to assess cellular toxicity and uptake and T cell activation, and (3) in-vivo studies to assess bio-distribution. C_FIG