Sequence-Controlled Delivery of Peptides from Hierarchically Structured Nanomaterials

Peptide drugs delivered orally need to be protected from degradation for achieving their functions. To fulfill the complicated task of oral drug delivery, we present a hierarchically structured drug-delivery system that can undertake structural changes, so multiple functions can be triggered by a sequence of stimuli. Such hierarchical system is achieved in a nanoparticle-in-nanofiber configuration, in which both the nanofibers and the nanoparticles are pH-responsive and biocompatible. A model peptide is efficiently encapsulated under mild condition, and the nanocarriers are further electrospun with a pH-responsive mucoadhesive polymer. The nanoparticles are released from the nanofibers, and thereafter the peptides are released from the nanoparticles in a pH-responsive manner. The nanoparticles are compatible with caco-2 cells, and the endocytosis of the nanoparticles is described in detail

Nanocarrier for Oral Peptide Delivery Produced by Polyelectrolyte Complexation in Nanoconfinement

The hydrophilic peptide YY (PYY) is a promising hormone-based antiobesity drug. We present a new concept for the delivery of PYY from pH-responsive chitosan-based nanocarriers. To overcome the drawbacks while retaining the merits of the polyelectrolyte complex (PEC) method, we propose a one-pot approach for the encapsulation of a hydrophilic peptide drug in cross-linked PEC nanocarriers. First, the hydrophilic peptide is encapsulated via polyelectrolyte complexation within water-in-oil miniemulsion droplets. In a second step, the PEC surface is reinforced by controlled interfacial cross-linking. PYY is efficiently encapsulated and released upon pH change. Such nanocarriers are promising candidates for the fight against obesity and, in general, for the oral delivery of protein drugs