Non-viral nanoparticle-based delivery system

A method of making a polymeric delivery system for nucleic acids and/or anticancer drugs,

• wherein the polymeric delivery system comprises nanoparticles comprising:
• a plurality of cationic chitosan polymers, polyethylene glycol and a peptide sequence, and wherein the peptide sequence comprises a cell penetrating peptide, a protein transduction domain, and a cell surface receptor targeting moiety,
• and the polymeric delivery system is made by a method comprising:
• a. reacting amine groups of chitosan with phthalic anhydride as a protection step;
• b. activating monomethoxy polyethylene glycol (mPEG-OH) with succinic anhydride to form mPEG-COOH;
• c. Activation of mPEG-COOH with thionyl chloride to form mPEG-COCl to form an activated PEG;
• d. reacting hydroxyl groups of chitosan to the activated mPEG-COCl to form PEGylated chitosan;
• e. reacting monomethoxy group of PEGylated chitosan with aluminium chloride in ethane thiol to convert methoxy to hydroxyl group;
• f. reacting hydroxyl terminated PEGylated chitosan with succinic anhydride to form an activated Chitosan-PEG-COOH;
• g. reacting activated Chitosan-PEG-COOH with amine terminated peptide (TAT/MGF/CP15) using EDC and DMAP as a catalyst to form Chitosan-PEG-Peptide;
• and
• h. reacting Chitosan-PEG-Peptide with hydrazine monohydrate to deprotect amine groups of chitosan,
• and wherein the plurality of cationic chitosan polymers are cross linked to each other to form the outer layer of the nanoparticle to generate an internal core;
• and the non-viral nanoparticle has an average diameter of between about 5 to 300 nm.