Phosphate-crosslinked starch nanoparticles and use for drug delivery

Abstract

This specification describes a nanoparticle delivery agent for drugs such as chemotherapy drugs. Starch nanoparticles are internally crosslinked by a phosphate crosslinker such as sodium trimetaphosphate (STMP) using a phase inversion emulsion process. The particle size may be in the range of 80-500 nm. A wide variety of organic phosphates are present apart from the phosphodiester crosslinking. These included triphosphates, monophosphates and diphosphates. The nanoparticles are hydrogels and retain significant amounts of water when dispersed in solution possibly due to the electrostatic repulsion between the chains within the nanoparticle. The nanoparticles are, in general, non-toxic, for example to HeLa cancer cells. The nanoparticles display a high drug loading, with a maximum seen with about 20-40 mol % STMP. Drug release occurs more readily at lower pH. Exposure to typical cell culture environments induces significant release of drug compared to simple buffer environments.

We claim: 
     
         1 . A nanoparticle comprising starch strands crosslinked with a phosphate crosslinker. 
     
     
         2 . The nanoparticle of  claim 1  having a peak intensity or Z-average size determined by DLS in the range of 80-500 nm. 
     
     
         3 . The nanoparticle of  claim 1  with a chemotherapeutic drug loaded into the nanoparticle. 
     
     
         4 . The nanoparticle of  claim 1  with a targeting ligand. 
     
     
         5 . The nanoparticle of  claim 1  made with 20-50 mol % STMP. 
     
     
         6 . A process of treating a disease of the nose, mouth or throat comprising a step of applying a nanoparticle of  claim 1  to the nose, mouth or throat, or of treating a cancer comprising a step of injecting nanoparticles according to  claim 1  into blood of an animal, which may be a human. 
     
     
         7 . A process of making nanoparticles using a phase inversion emulsion process wherein starch is is cross-linked with a phosphate cross-linker. 
     
     
         8 . The process of  claim 7  wherein a drug is included in the water phase. 
     
     
         9 . The process of  claim 7  wherein the crosslinker is STMP.