Multilayer nanoarchitectonics of polypeptide capsules with size-selective permeability

This work presents the fabrication and characterization of hollow nanocapsules prepared by Layer-by-Layer (LbL) assembly of the biocompatible polypeptides poly(l-lysine) (PLL) and poly(glutamic acid) (PGA) on liposomal soft templates. Sequential adsorption of oppositely charged polypeptides onto 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes, followed by surfactant-mediated disruption of the lipid bilayer, yield hollow polypeptide capsules. Multilayer growth and charge reversal were monitored by zeta potential and dynamic light scattering (DLS), while capsule morphology and integrity after template removal were assessed by atomic force microscopy (AFM). The permeability of the polypeptide shells was investigated using the pH-sensitive dye 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and the hydrophilic fluorescent probe calcein. Proton diffusion experiments with encapsulated HPTS reveal rapid ionic transport across the multilayer shells, whereas diffusion of the larger hydrophilic probe calcein is strongly retarded, establishing an operational size-selective permeability regime where small ions permeate freely while larger solutes experience significant transport resistance. These contrasting transport behaviors suggest a species-dependent permeability may can be rationalized in terms of the hierarchical organization and dynamic hydration of the polypeptide multilayers. The results provide mechanistic insight into transport regulation in biocompatible multilayer capsules and establish a foundation for the rational design of polypeptide-based carriers with tunable permeability characteristics.