Cellulose-based nanoparticles for drug delivery

Abstract

In one aspect, there is provided a compound comprising an acetylated carboxymethylcellulose (CMC-Ac) covalently linked to: at least one poly(ethylene glycol) (PEG), and at least one hydrophobic drug. In another aspect, a self-assembling nanoparticle composition comprising such compounds is provided.

1 . A method of treating cancer in a patient in need thereof, comprising administering to said patient an effective amount of a self-assembling nanoparticle composition comprising compound comprising an acetylated carboxymethylcellulose (CMC-Ac) covalently linked to: at least one poly(ethylene glycol) (PEG), and at least one anticancer agent. 
     
     
         2 . The method as defined in  claim 1 , wherein the cancer is selected from breast cancer, lung cancer, metastatic cancer, and pancreatic cancer. 
     
     
         3 . The method of  claim 1 , wherein the covalent linkages are ester linkages. 
     
     
         4 . The method of  claim 1 , wherein the at least one hydrophobic drug is one of docetaxel, camptothecin and paclitaxel. 
     
     
         5 . A process for preparing a self-assembling nanoparticle composition comprising:
 a) covalently linking at least one PEG and at least one hydrophobic drug to a CMC-Ac;   b) isolating the product of step (a);   c) dissolving the isolated product of step (b) in a suitable organic solvent, preferably DMF or DMSO and further preferably THF or acetonitrile, to form a solution;   d) adding the solution of step (c) dropwise to an aqueous solution under conditions suitable for forming the self-assembling nanoparticle composition.   
     
     
         6 . The process as claimed in  claim 5 , wherein the covalent linkages are ester linkages. 
     
     
         7 . The process as claimed in  claim 5 , wherein said suitable conditions in step (d) comprise vigorously mixing said aqueous solution during the dropwise addition of the solution of step (c). 
     
     
         8 . The process as claimed in  claim 5 , wherein the solution of step (c) has a concentration of 10-25 mg/mL. 
     
     
         9 . The process as claimed in  claim 8 , wherein the solution of step (c) has a concentration of 10 mg/mL. 
     
     
         10 . The process as claimed in  claim 5 , wherein step (d) comprises a 10-fold dilution of the solution of step (c) once the addition to the aqueous solution is complete. 
     
     
         11 . The process as claimed in  claim 5 , further comprising isolating the self-assembling nanoparticle composition formed in step (d) via dialysis and/or filtration. 
     
     
         12 . The process as claimed in  claim 5 , wherein the at least one hydrophobic drug is one of docetaxel, camptothecin and paclitaxel. 
     
     
         13 . The process as claimed in  claim 12 , wherein the CMC-Ac is prepared via acetylation of a carboxymethyl cellulose with a degree of substitution (DS) of between about 0.75 and about 0.85, preferably about 0.82. 
     
     
         14 . The process as claimed in  claim 13 , wherein the at least one PEG is poly(ethylene glycol) methyl ether (mPEG) having an average M n  of between about 550 and about 10,000, preferably about 2000. 
     
     
         15 . The process as claimed in  claim 14 , wherein step (a) comprises providing the mPEG in an amount of about 30 mol % and providing the docetaxel in an amount of about 40-50 mol %, relative to the carboxylic acid groups of said CMC-Ac, preferably about 40 mol % or 50 mol %. 
     
     
         16 . The process as claimed in  claim 5 , wherein the solution of step (c) further comprises at least one hydrophobic agent encapsulated therein, preferably selected from either an imaging agent or a therapeutic agent. 
     
     
         17 . The process as claimed in  claim 16 , wherein the at least one imaging agent is a superparamagnetic iron oxide nanoparticle (SPION). 
     
     
         18 . The process as claimed in  claim 17 , wherein the at least one imaging agent is present in the solution of step (c) in an amount of about 9-50 weight %, based on the combined weight of the at least one imaging agent and the isolated product of step (b).