DS0305 - Nanomatériaux et nanotechnologies pour les produits du futur

PREcipitation of Artificial Structural PROteins and POlySAccharides into nanocapsuLes – PREPROPOSAL

Submission summary

This French-Singaporean international project, PREPROPOSAL, addresses the development of biorelevant sub-100 nm functional biopolymer-based nanocapsules for drug delivery applications.

PREPROPOSAL aims at mastering the nanoprecipitation process, an extremely easy-to-handle methodology that holds great promises in nanomedicine, to conceive stimuli-responsive biodegradable protein/polysaccharide nanocapsules displaying high structural integrity and tunable diffusion barrier properties in benign conditions.The rationale of this process lies in the supersaturation of a hydrophobic solute (oil for instance) initially dissolved in a water-miscible solvent when a large excess of the nonsolvent, water is added, leading, under appropriate conditions, to the spontaneous formation of the dispersion of nanodroplets.

Herein, the “one-pot” fabrication of advanced nanomaterials through nanoprecipitation will rely on the use of precisely-defined silk-like recombinant suckerin proteins produced in E. coli in combination with non-immunogenic polysaccharides.
Careful exploration of protein/water/organic solvent, polysaccharide/water/organic solvent and oil/water/ organic solvent ternary systems and overlap of the resulting phase diagrams will first allow for identifying conditions of solvent displacement for which a dispersion of nanoscale oil droplets with narrow size distribution is generated and the polymers inclined to lie on the surface of the oil nanodroplets (acting as templates) to give rise to robust nanocapsules.
The loading of the nanocapsules will also be performed in the course of the nanoprecipitation process by incorporating hydrophobic actives (prone to diffuse in the oily core) directly in the initial organic solution.

Thanks to the propensity of the suckerin proteins to refold into ß-sheets enriched structures promoting the reinforcement of the polymer walls and to the presence of numerous functions of biological interest on the polysaccharide chains (ligands, fluorophore…), loaded functional nanocapsules with excellent mechanical stability and tunable permeability will be straightforwardly constructed.

Properties of the resulting nanocapsules in terms of biodegradability, permeability or stiffness and release kinetics will be finally monitored by modulating the sequence of the proteins through controlled incorporation of specific motifs inducing proteolysis, pH responsiveness (Di-Hydroxylphenyalanine) or capable to undergo covalent cross-linking reactions (tyrosine), or by tuning the polysaccharide/protein ratio and/or the methodology of nanoprecipitation (i.e. co-precipitation or sequential precipitations of the biopolymers).

As the generation of functional protein-based nanocapsules by nanoprecipitation has never been addressed so far, the envisioned results will constitute a major advance in the field of drug delivery devices.

Project coordination

Julien BERNARD (Institut National des Sciences Appliquées de Lyon - Laboratoire d'Ingénierie des Matériaux Polymères)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Nanyang Technological University School of Materials Science and Engineering
INSA de Lyon - IMP Institut National des Sciences Appliquées de Lyon - Laboratoire d'Ingénierie des Matériaux Polymères

Help of the ANR 245,200 euros
Beginning and duration of the scientific project: October 2015 - 36 Months

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