Development of M cell-targeting starch-based nanomicelles for oral delivery of immunoactive peptides

Abstract

We prepared nine residue peptide CKSTHPLSC (CKS9)-grafted starch stearate for the simultaneous realization of tyrosinase related protein-2 (Trp-2) shielding and microfold cell (M cell) targeting. The suited introduction of CKS9 and stearic acid endowed the prepared nanomicelles (200 ~ 250 nm) with the lower critical micelle concentration (0.0209 mg/mL) and affinity constant (2.10 ×10−7), robust encapsulation efficiency (61.59 ~ 72.23%) and loading capacity (49.43 ~ 55.71%), controllable release of Trp-2 peptide, excellent structure stability against the changes of physiological conditions, ultra-dilution and long-term storage. Approx.72% of the loaded cargos went through apical-to-basolateral transportation. The M cell targeting affinity of the designed micelles is 1.5 times stronger than that towards Caco-2 cells. All these performances can be ascribed to the special framework of the designed polymer, namely, the hydrophobic stearic acid side chains and stable M cell-targeting ligand with a higher proportion of hydrophilic domain, which ensured the formation of steady core-shell spherical nanomicelles and the full exposure of targeting ligand. These rationally designed micelles provide a promising potential for developing stable and effective drug delivery systems applicable for oral immunization.