Production of natural-derived polymers for delivery of nucleic acids
DURÉE DU PROJET:
COÛT DU PROJET:
CONTRIBUTION DE PRIMA:
DÉTAILS DU PROJET:
As mentioned above, current production methods of chitosan and NAs must be modified to be amenable to scale-up and to cGMP compliance. The production of medical grade chitosans and their characterization is particularly technically challenging (even more for a modified chitosan), partly since the natural-derived polymer is inherently polydisperse but also because of the strict requirements associated with cGMP production. CS/NA polymeric nanoparticles are currently prepared by manual mixing of small volumes of dilute chitosan and nucleic acid solutions. These polymeric nanoparticle preparations must be used within a few hours post-mixing and are prone to aggregation in physiological conditions. Improvement of the preparation methods and of the polymeric nanoparticles properties is required to increase the quantity and the reproducibility of these products and to significantly broaden their applicability.
The specific technological limits that this project will resolve are:
- As mentioned above the production of a medical grade chitosans by procedures that are amenable to scale-up and to cGMP compliance is technically challenging. The same challenge applies to the production of modified chitosans. Relying on our established expertise in chitosan science, we will develop innovative, robust and reproducible methods for preparation and characterization of such chitosans that are cGMP compliant.
- The strict requirements associated with the production of pDNA using processes that are amenable to cGMP compliance represents a challenge that will be tackled by implementing production processes as well as analytical procedures within a quality system.
- The volume of polymeric nanoparticles produced currently by manual mixing will be increased by developing an automated in-line mixing system.
- The limited stability of polymeric nanoparticles in aqueous suspension will be overcome by developing freeze-drying methods for long-term storage and easy distribution of these products.
- The NA concentration and quantity limitations resulting from the requirement of mixing at low concentration will be overcome by developing concentration methods relying of freeze-drying and tangential flow filtration.
- The colloidal instability of polymeric nanoparticles in physiological conditions will be overcome by developing of a new family of block copolymers comprised of CS and polyethylene glycol (CS-PEG block copolymer). The use of such block copolymers will additionally facilitate the inclusion of ligand moieties in the polymeric nanoparticles for applications where targeting is required.
PARTENAIRES DE RECHERCHE: