Multi-Functional Micro and Nanoparticles for Use in Root Canal Therapies

Abstract

Chitosan nanoparticles are provided for use in the in vivo treatment of connective tissues in root canal therapies. The nanoparticles are optionally linked with one or more photoactivatable compounds for providing antibactenal/antibiofilm properties, neutralizing bacterial byproducts and/or chemical/photodynamic crosslinking to achieve enhanced mechanical properties, chemical stability in connective tissues and/or to improve surface/interfacial integrity between filling material and connective tissue.

1 . A composition for use in in vivo disinfection and/or remineralization treatment of connective or hard tissues comprising multifunctional bioactive nanoparticles,
 said nanoparticles comprising a polysaccharide having a plurality of five or six membered ring carbohydrate monomers, where each said monomer is optionally substituted with at least one of a primary amine and a secondary or tertiary amine having an acyl group with two to seven carbon atoms.   
     
     
         2 . The composition of  claim 1 , wherein said polysaccharide (chitosan) nanoparticles are formed spontaneously by interaction with sodium tripolyphosphate. 
     
     
         3 . The composition of  claim 2 , wherein said polysaccharide nanoparticles comprise a photoactivatable moiety. 
     
     
         4 . The composition of  claim 3 , wherein said photoactivatable moiety is Rose Bengal or a flavin mononucleotide bonded to said reactive amine group of polymeric nanoparticles using a chemical crosslinker carbodiimide. 
     
     
         5 . The composition of  claim 4  for use in endodontic therapies as a precursor to root canal filing, and wherein the connective or hard tissues comprises dentin. 
     
     
         6 . The composition of  claim 4  for use with a multifunctional therapy of eliminating bacteria as well as stabilizing dentin in root treated teeth. 
     
     
         7 . The composition of  claim 1 , wherein said connective tissues comprise dentin collagen and said bioactive nanoparticle comprise polymeric nanoparticles which are photoactivatable to leave the polymeric nanoparticle incorporated in the dentin collagen. 
     
     
         8 . The composition of  claim 5 , wherein said polysaccharide comprises a linear polysaccharide of said monomers linked with a β-1,4 glycosidic bond. 
     
     
         9 . The composition of  claim 8 , wherein each said amine is bonded to a carbon atom adjacent to an anomeric carbon atom of said monomer. 
     
     
         10 . The composition of  claim 5 , wherein said acyl group is an acetyl group. 
     
     
         11 . The composition of  claim 5 , wherein each said monomer is D-glucosamine or N-acetyl-D-glucosamine. 
     
     
         12 . The composition of  claim 5 , wherein said polysaccharide comprises 75% or 85% by weight of said D-glucosamine and 15% to 25% of said N-acetyl-D-glucosamine. 
     
     
         13 . A method of dental restoration whereby following exposure of dentin, contacting said dentin with the composition of  claim 1 . 
     
     
         14 . The method of  claim 13 , wherein said nanoparticles comprise a polymer represented by the general formula (1) 
       
         
           
           
               
               
           
         
         where η is an integer. 
       
     
     
         15 . The method of  claim 13 , wherein following said step of contacting said dentin, exposing said nanoparticles to light energy of a period of between 6 minutes and 12 minutes to effect at least partial crosslinking between said polymeric nanoparticles and adjacent dentin tissue mainly collagen. 
     
     
         16 . The method of  claim 15 , wherein said light energy comprises visible range light energy. 
     
     
         17 . The method of  claim 16 , wherein the dental restoration comprises an endodontic treatment, said method further comprising:
 prior to said step of contacting said dentin, removing tooth pulp from a tooth root to form a hollowed-out root canal, whereby said dentin is exposed along a substantial length of said hollow root canal; and   after exposing said compound to said light energy, filling said hollowed-out root canal with a filling material.   
     
     
         18 . The method of  claim 17 , wherein said filling material comprises gutta-percha rubber. 
     
     
         19 . The method of  claim 13 , wherein said step of contacting said dentin comprises at least one irrigation or application of the said dentin. 
     
     
         20 . A method of making a medicament for in vivo disinfection and remineralization of hard or connective tissues, comprising:
 forming phosphorylated chitosan polymer; and   micronizing said phosphorylated chitosan polymer to form nanoparticles having an average size selected at between about 40 microns and about 80 microns, and admixing said nanoparticles with a pharmaceutically acceptable carrier.   
     
     
         21 . The method of  claim 20 , wherein said pharmaceutically acceptable carrier is selected from the group consisting of water and an alcohol. 
     
     
         22 . The method of  claim 20 , wherein prior to forming said nanoparticles associating phosphorylated chitosan with a photoactivatable moiety. 
     
     
         23 . The method of  claim 22 , wherein the hard and connective tissue comprises dentin. 
     
     
         24 . The method of  claim 23 , wherein the photoactivatable moiety comprises Rose Bengal. 
     
     
         25 . A method of making a medicament for in vivo disinfection and remineralization of hard or connective tissues, comprising:
 forming phosphorylated chitosan polymer; and   micronizing said phosphorylated chitosan polymer to form nanoparticles having an average size selected at up to about 100 nanometers, and preferably between about 60 nanometers and 90 nanometers, and admixing or mixing said nanoparticles with a pharmaceutically acceptable carrier.   
     
     
         26 . The method as claimed in  claim 25 , wherein said medicament is in the form of a solution and said pharmaceutically acceptable carrier comprises a liquid. 
     
     
         27 . The method of  claim 26 , wherein said pharmaceutically acceptable carrier is selected from the group consisting of water and an alcohol. 
     
     
         28 . The method of  claim 25 , wherein prior to forming said nanoparticles associating phosphorylated chitosan with a photoactivatable moiety. 
     
     
         29 . The method of  claim 28 , wherein the hard and connective tissue comprise dentin. 
     
     
         30 . The method of  claim 29 , wherein the photoactivatable moiety comprises Rose Bengal. 
     
     
         31 . The method of  claim 30 , wherein said phosphorylated chitosan polymer is represented by the general formula (1) 
       
         
           
           
               
               
           
         
         where η is an integer.