Controlling the complexation of polysaccharides into multi-functional colloidal assemblies for nanomedicine

• Colloidal chitosan complexes by controlled assembly of heparin or dextran sulfate.
• Long-term stability in water, PBS and acidic medium.
• Molecular drug successfully encapsulated.
• Various antibodies sorbed at the particle interface with conservation of activity.
• Multifunctional nanodelivery systems formed by polyelectrolyte controlled assembly.

The controlled assembly of oppositely charged polysaccharides led to colloids stable in physiological media, capable of encapsulating a molecular drug and of sorbing proteins at their interface. Two types of particles were obtained: both chitosan–dextran sulfate (CS–DS) and chitosan–heparin (CS–HP) stable over 30 days in PBS at 25 and 37 °C. At gastric pH 1.2, these particles remained stable over 3 days, enough for a stomach transit. The structural analysis by small angle X-ray scattering (SAXS) showed that CS–DS surface was semi-rough and chains inside particle exhibited rod-like conformation. Moreover, the particle interfaces could efficiently be functionalized with anti-OVA or anti-α4β7 antibodies, in PBS, with the conservation of the antibody bioactivity over at least 8 days. Finally, during the assembly process, a molecular model drug, AMP, could be encapsulated with a loading efficiency up to 72% for CS–DS particles and 66% for CS–HP. All these data establish that the controlled assembly process under equilibrium conditions lead to colloids well suited for the targeted nanodelivery of drugs.

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