Non-viral nanoparticle-based delivery system

Abstract

The present invention concerns a polymeric material for the production of a non-viral nanoparticle. The polymeric material comprises (i) a hydrophilic linear polymer having a first end and a second end, (iii) a cross-linkable cationic polymer covalently bonded to the first end of the hydrophilic linear polymer, and (iii) at least one targeting/penetrating peptide covalently associated to the second end of the hydrophilic linear polymer. Also disclosed herein are nanoparticles produced with these polymeric material, processes for making the polymeric material and the nanoparticles as well as use of the nanoparticles.

What is claimed is: 
     
         1 . A polymeric material of a non-viral nanoparticle, said polymeric material comprising:
 (i) a linear polyethylene glycol polymer having a first end and a second end,   (ii) a cross-linkable cationic chitosan polymer covalently associated to the first end of the linear polyethylene glycol polymer, and   (iii) at least one targeting/penetrating peptide covalently associated to the second end of the linear polyethylene glycol polymer.   
     
     
         2 . The polymeric material of  claim 1 , wherein the linear polyethylene glycol polymer has an average molecular weight between about 1 000 to about 5 000 Da. 
     
     
         3 . The polymeric material of  claim 1 , wherein the cross-linkable cationic chitosan polymer has an average molecular weight of about 10 to about 200 000 Da. 
     
     
         4 . The polymeric material of  claim 1 , wherein the cross-linkable cationic chitosan polymer has a degree of deacetylation of about 75 to about 85%. 
     
     
         5 . The polymeric material of  claim 1 , wherein the at least one targeting/penetrating peptide can bind to a cell surface or cell-associated receptor or can facilitate the translocation of the non-viral particle across a biological or a cellular membrane. 
     
     
         6 . A non-viral nanoparticle comprising:
 (i) a plurality of polymeric materials according to  claim 1 , wherein the cationic polymer is cross-linked so as to form an internal core; and   (ii) an anionic agent entrapped in the internal core.   
     
     
         7 . The non-viral nanoparticle of  claim 6 , wherein the anionic agent is a nucleic acid molecule. 
     
     
         8 . The non-viral nanoparticle of  claim 7 , wherein the nucleic acid molecule is a short interfering RNA (siRNA). 
     
     
         9 . The non-viral nanoparticle of  claim 6  having a diameter between about 5 nm to about 100 nm. 
     
     
         10 . The non-viral nanoparticle of  claim 6 , wherein the plurality of polymeric materials comprises a first polymeric material having a first targeting/penetrating peptide that can bind to a cell surface or cell-associated receptor and a second polymeric material having a second targeting/penetrating peptide that can facilitate the translocation of the non-viral particle across a cellular membrane. 
     
     
         11 . A method of delivering an anionic agent to a cell, said method comprising contacting the non-viral nanoparticle of  claim 6  with the cell under conditions sufficient for allowing the anionic agent to enter the cell. 
     
     
         12 . The method of  claim 11 , wherein the cell is in vitro. 
     
     
         13 . The method of  claim 11 , wherein the cell is to be introduced into an individual in need thereof. 
     
     
         14 . The method of  claim 14 , wherein the cell is in an individual in need thereof. 
     
     
         15 . The method of  claim 14 , further comprising formulating the non-viral nanoparticle for intranasal administration prior to contacting the individual. 
     
     
         16 . The method of  claim 14 , wherein the cell is in a brain of the individual. 
     
     
         17 . The method of  claim 16  for the prevention, treatment and/or alleviation of symptoms associated to a neurodegenerative disease or a brain cancer. 
     
     
         18 . The method of  claim 17 , wherein the neurodegenerative disease is selected from the group consisting or spinocerebellar ataxia, Huntington's disease, Parkinson's disease, Alzheimer's disease, dementia and amyotrophic lateral sclerosis. 
     
     
         19 . The method of  claim 14 , further comprising formulating the non-viral nanoparticle for intravenous administration prior to contacting the individual. 
     
     
         20 . The method of  claim 19  for the prevention, treatment and/or alleviations of symptoms associated with a proliferative disease.