Aptamer bioconjugate drug delivery device

Abstract

A delivery device for an active agent comprises nanoparticles based on a biopolymer such as starch. The delivery device may also be in the form of an aptamer-biopolymer-active agent conjugate wherein the aptamer targets the device for the treatment of specific disorders. The nanoparticles may be made by applying a high shear force in the presence of a crosslinker. The particles may be predominantly in the range of 50-150 nm and form a colloidal dispersion of crosslinked hydrogel particles in water. The biopolymer may be functionalized. The aptamer may be conjugated directly to the cross-linked biopolymers. The active agent may be a drug useful for the treatment of cancer. The delivery device survives for a period of time in the body sufficient to allow for the sustained release of a drug and for the transportation and uptake of the conjugate into targeted cells. However, the biopolymer is biocompatible and resorbable.

We claim: 
     
         1 . A medicament comprising,
 a) nanoparticles comprising a mass of crosslinked polymers, at least 50% of the polymers being high molecular weight starch; and,   b) active agent molecules conjugated with the nanoparticles.   
     
     
         2 . The medicament of  claim 1  wherein the nanoparticles have a number average size in the range of 50-150 nm when measured by any of SEM, NTA or DLS. 
     
     
         3 . The medicament of  claim 2  wherein most of the nanoparticles have a size in the range of 50-150 nm when measured by any of SEM, NTA or DLS. 
     
     
         4 . The medicament of  claim 1  wherein the active agent comprises a drug. 
     
     
         5 . The medicament of  claim 4  wherein the the drug is a chemotherapeutic drug. 
     
     
         6 . The medicament of  claim 1  wherein the zeta potential of the nanoparticles is negative. 
     
     
         7 . The medicament of  claim 1  wherein the nanoparticles further comprises ligands conjugated to the cross-linked starch ploymers. 
     
     
         8 . The medicament of  claim 7  wherein the ligands are aptamers. 
     
     
         9 . A method of making a medicament comprising the steps of,
 a) forming a plurality of nanoparticles, the nanoparticles comprising a mass of crosslinked polymers, at least 50% of the polymers being amylose, amylopectin, or a mixture of amylose and amylopectin; and,   b) combining an active with the nanoparticles.   
     
     
         10 . The method of  claim 9  further comprising a step of functionalizing the nanoparticle such that the nanoparticle has a zeta potential of negative 10 mV or a more negative zeta potential. 
     
     
         11 . The method of  claim 9  wherein step b) comprises phase separation or precipitation in ethanol. 
     
     
         12 . The method of  claim 11  further comprising a step of lyophilization. 
     
     
         13 . The method of  claim 9  comprising a step of oxidizing the cross-linked starch polymers. 
     
     
         14 . The method of  claim 13  wherein the polymers are oxidized by exposing the polymers to an oxidant in the presence of 2,2,6,6-tetramethylpiperidin-1-oxyl radicals. 
     
     
         15 . The method of  claim 9  further comprising functionalizing the nanoparticles with carboxyl functional groups. 
     
     
         16 . The method of  claim 15  further comprising attaching an aptamer to the polymers by a carboxyl-amine linkage.