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.