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 antibacterial/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.

What is claimed is: 
     
         1 . A composition for endodontic or dental restorative use, comprising:
 multifunctional biopolymer-based particles wherein a first portion of biopolymer-based particles have biopolymer repeat units covalently functionalized with photosensitizer moieties and a second portion of the of biopolymer-based particles have biopolymer repeat units covalently functionalized with phosphorylated moieties; and   a pharmaceutically acceptable liquid carrier, wherein the multifunctional biopolymer-based particles are mixed with the pharmaceutically acceptable liquid carrier to form a slurry.   
     
     
         2 . The composition of  claim 1  wherein the first portion of biopolymer-based particles correspond to the second portion of biopolymer-based particles, such that the biopolymer-based particles are functionalized with both the photosensitizer moieties and the phosphorylated moieties. 
     
     
         3 . The composition of  claim 1  wherein the biopolymer is any one of chitosan and chitosan-based derivatives. 
     
     
         4 . The composition of  claim 1  wherein the photosensitizer moieties are any one of an anionic photosensitizer, a cationic photosensitizer, a porphyrin, and photosensitizers that contain a free reactive group in its chemical structure, and wherein the photosensitizer moieties are selected to produce singlet oxygen upon photodynamic therapy. 
     
     
         5 . The composition of  claim 2  wherein the photosensitizer moieties are anionic photosensitizers. 
     
     
         6 . The composition of  claim 5  wherein the anionic photosensitizer is any one of Rose Bengal and Flavin. 
     
     
         7 . The composition of  claim 1  wherein the multifunctional biopolymer-based particles have a diameter from about 40 nm to about 150 nm. 
     
     
         8 . The composition of  claim 1  wherein the multifunctional biopolymer-based particles are in an amount of about 0.3 to 1% (by weight). 
     
     
         9 . The composition of  claim 1  wherein the pharmaceutically acceptable liquid carrier is any one of water and an alcohol. 
     
     
         10 . The use of the composition of  claim 1  as an antibiofilm agent for elimination and/or prevention of bacterial biofilm. 
     
     
         11 . The use of the composition of  claim 1  as an endodontic agent for pre-treatment of dentin tissues. 
     
     
         12 . The use of the composition of  claim 1  in management of dentin caries. 
     
     
         13 . The use of the composition of  claim 1  as a remineralization agent. 
     
     
         14 . The composition of  claim 6  wherein the multifunctional biopolymer-based particles have a diameter between about 40 nm to 90 nm. 
     
     
         15 . The use of the composition of  claim 1  as a stabilization agent for stabilizing or improving dentin mechanical and chemical properties. 
     
     
         16 . A method of dental treatment, comprising:
 contacting a dentin of a tooth with a pharmaceutical composition comprising a slurry of biopolymer-based particles wherein a first portion of biopolymer-based particles have biopolymer repeat units covalently functionalized with photosensitizer moieties and a second portion of the of biopolymer-based particles have biopolymer repeat units covalently functionalized with phosphorylated moieties; and   exposing the slurry of biopolymer-based particles to a light having a wavelength selected to activate the photosensitizer moieties for a period of time sufficient to crosslink the biopolymer-based particles functionalized with the photosensitizer moieties to the dentin.   
     
     
         17 . The method of  claim 16  wherein the first portion of biopolymer-based particles correspond to the second portion of biopolymer-based particles, such that the biopolymer-based particles are functionalized with both the photosensitizer moieties and the phosphorylated moieties. 
     
     
         18 . A method of dental treatment, comprising:
 removing infected pulp tissue from a tooth root and forming a hollowed-out root canal thereby exposing dentin along a substantial length of the hollowed-out root canal;   applying a slurry of biopolymer-based particles to the exposed dentin within the hollowed-out root canal, wherein a first portion of biopolymer-based particles have biopolymer repeat units covalently functionalized with photosensitizer moieties and a second portion of biopolymer-based particles have biopolymer repeat units covalently functionalized with phosphorylated moieties;   exposing the slurry of biopolymer-based particles to a light having a wavelength selected to activate the photosensitizer moieties for a period of time; and   after exposing the slurry to the light, filling the hollowed-out root canal with a filling material.   
     
     
         19 . The method of  claim 18  wherein the first portion of biopolymer-based particles correspond to the second portion of biopolymer-based particles, such that the biopolymer-based particles are functionalized with both the photosensitizer moieties and the phosphorylated moieties. 
     
     
         20 . The method of  claim 18  further comprising the step of cleaning and shaping the hollowed-out root canal. 
     
     
         21 . The method of  claim 18  wherein the period of time of exposure to the light is from about 2 minutes to about 12 minutes. 
     
     
         22 . The method of  claim 18  further comprising the step of washing the hollowed-out root canal following photoactivation of the photosensitizer moieties.