Nano-structured and functionalized materials for encapsulation, transport, targeting and controlled release of drugs are of high interest to overcome low bioavailability in oral administration. We develop lipid-based cubosomes, which are surface-functionalized with biocompatible chitosan-N-arginine and alginate, displaying internal liquid crystalline structures. Polyelectrolyte-shell (PS) cubosomes have pH-responsive characteristics profitable for oral delivery. The obtained PScubosomes can strongly interact with serum albumin, a protein which is released in the stomach under gastric cancer conditions. An effective thermodynamic PScubosome-protein interaction was characterized at pH 2.0 and 7.4 by isothermal titration calorimetry at 37 °C. A high increment of the albumin conformation transition temperature was evidenced by differential scanning calorimetry upon incubation with PScubosomes. The performed structural studies by synchrotron small-angle X-ray scattering (SAXS) revealed essential alterations in the internal liquid crystalline topology of the nanocarriers including an Im3m to Pn3m transition and a reduction of the cubic lattice parameters. The PScubosome nanoparticle interaction with serum albumin, leading to inner structural changes in a range of temperatures, promoted the release of water from the cubosomal nanochannels. Altogether, the results revealed effective interactions of the PScubosomes with albumin under simulated gastrointestinal pH conditions and suggested promising nanocarrier characteristics for triggered oral drug release.

Institute of Chemistry State University of Campinas 13083 970 Campinas Brazil

Institute of Physics ELI Beamlines Academy of Sciences of the Czech Republic CZ 18221 Prague Czech Republic

Laboratory of Nano Bio Materials 04023 062 Sao Paulo Brazil

Université Paris Saclay CNRS Institut Galien Paris Saclay 91400 Orsay France

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Dynamic Self-Assembly and Stimuli-Responsive Disassembly of Bioactive-Loaded Cubosomes in Biomimetic Media Traced by Real-Time Small-Angle X-ray Scattering and Cryogenic Transmission Electron Microscopy