Supramolecular dextran/polyamine phosphate nanocapsules with smart responsiveness for encapsulation of therapeutics

The polyallylamine hydrochloride (PAH) polymer is here functionalized with branched and biocompatible polysaccharide dextran (DEX) molecules. Covalent conjugation of DEX to PAH has been achieved through a straightforward reductive amination approach, allowing for a controlled number of DEX chains per PAH polymer (PAH:DEXn, n = 0.1, 0.5, 1, 2, 5, 10). When exposed to phosphate buffer, PAH:DEXn polymers form supramolecular assemblies. Physico chemical characteristics and pH responsiveness of the assemblies are correlated with the number of dextran chains per PAH molecule. Nanocapsules (NCs) are formed when PAH:DEX ratio is 1. Capsule formation is explained by the branched nature of DEX and steric consideration ruling the organization of polyamine chains in phosphate buffer. NCs and glyconanoparticles formed with n < 1 are responsive to pH changes, being disassembled at endosomal pH < 6 and reassembled when 6 < pH < 9. Dynamic light Scattering (DLS), ζ-potential measurements, cryo-Electron Microscopy and Small Angle X-ray Scattering (SAXS) provided key information about their structure, morphology, size, polydispersity, surface charge, and stability over time. Protein entrapment into the NCs and pH-dependent release is demonstrated with bovine serum albumin (BSA) as model protein by diffusion measurements in fluorescence correlation spectroscopy (FCS), following changes in BSA conformation before and after triggering NC disassembly by circular dichroism (CD), and comparing NCs SAXS fingerprints with and without BSA. Our results show novel assemblies based on polyamine phosphate interactions with capacity of loading large molecules through the formation of capsules, which may find applications in the endosomal delivery of therapeutic proteins and enzymes.