Cubosomal lipid nanoassemblies with pH-sensitive shells created by biopolymer complexes: A synchrotron SAXS study

We report a strategy for sustainable development of pH-responsive cubic liquid crystalline nanoparticles (cubosomes), in which the structure-defining lyotropic nonlamellar lipid and the eventually encapsulated guest molecules can be protected by pH-sensitive polyelectrolyte shells with mucoadhesive properties. Bulk non-lamellar phases as well as pH-responsive polyelectrolyte-modified nanocarriers were formed by spontaneous assembly of the nonlamellar lipid monoolein and two biopolymers tailored in nanocom-plexes with pH-dependent net charge. The mesophase particles involved positively charged N-arginine-modified chitosan (CHarg) and negatively charged alginate (ALG) chains assembled at different biopoly-mer concentrations and charge ratios into a series of pH-responsive complexes. The roles of Pluronic F127 as a dispersing agent and a stabilizer of the nanoscale dispersions were examined. Synchrotron small-angle X-ray scattering (SAXS) investigations were performed at several N-arginine-modified chitosan/al-ginate ratios (CHarg/ALG with 10,15 and 20 wt% ALG relative to CHarg) and varying pH values mimicking the pH conditions of the gastrointestinal route. The structural parameters characterizing the inner cubic liquid crystalline organizations of the nanocarriers were determined as well as the particle sizes and sta-bility on storage. The surface charge variations, influencing the measured zeta-potentials, evidenced the inclusion of the CHarg/ALG biopolymer complexes into the lipid nanoassemblies. The polyelectrolyte shells rendered the hybrid cubosome nanocarriers pH-sensitive and influenced the swelling of their lipid phase core as revealed by the acquired SAXS patterns. The pH-responsiveness and the mucoadhesive features of the cubosomal lipid/polyelectrolyte nanocomplexes may be of interest for in vivo drug delivery applications. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

A sustainable development strategy for pH-responsive cubosomes was developed, where pH-sensitive polyelectrolyte shells protect the structure of nanoparticles with mucoadhesive properties. The cubosomes exhibit pH-responsiveness and mucoadhesive features, making them potentially useful for in vivo drug delivery applications.