Highly loaded metal oxide materials by self-assembly for extended biologically active molecule release in medical and dental applications

Abstract

A biocompatible composite material for controlled release is disclosed, comprising a biocompatible metal oxide structure with a loaded network of pores. The pore network of the biocompatible composite material is filled with a uniformly distributed biologically active micellizing amphiphilic molecule, the size of these pores ranging from about 0.5 to about 100 nanometers. The material is characterized in that when exposed to phosphate-buffered saline (PBS), the controlled release of the active amphiphilic molecule is predominantly diffusion-driven over time.

What is claimed is: 
     
         1 . A biocompatible composite material for controlled release, comprising:
 a biocompatible metal oxide structure containing a network of pores, said pores containing a biologically active agent, wherein the biologically active agent has a biocompatibility index of greater than 1, and wherein the active agent has amphiphilic characteristics resulting in micellization when placed in aqueous conditions.   
     
     
         2 . The composite material of  claim 1 , wherein the biologically active agent is a pharmaceutical drug, a pharmaceutical conjugated drug, a pharmaceutical prodrug, an antimicrobial, an antiseptic agent, an antifungal agent, a peptide, DNA or combinations thereof. 
     
     
         3 . The composite material of  claim 1 , wherein the biologically active agent is an antimicrobial agent. 
     
     
         4 . The composite material of  claim 1 , wherein the biologically active agent is any one of octenidine dihydrochloride, polyhexamethylene biguanide, cetylpyridinium chloride or lauric arginate. 
     
     
         5 . The composite material of  claim 1  wherein the biologically active agent comprises octenidine or a salt thereof. 
     
     
         6 . The composite material of  claim 1  having a controlled release of the biologically active agent from the composite material in phosphate-buffered saline (PBS), wherein the rate of release is predominantly driven by the diffusion of the biologically active agent out of the metal oxide structure. 
     
     
         7 . The composite material of  claim 1 , wherein said biocompatible metal oxide comprises any of the following metal oxides: silicon dioxide, organosilicates, aluminosilicate, aluminum oxide, calcium phosphate, titanium dioxide, and zinc oxide. 
     
     
         8 . The composite material of  claim 1 , wherein the composite material is incorporated into a polymer, a resin, or a resin composite. 
     
     
         9 . The composite material of  claim 8 , wherein the polymer, resin, or resin composite comprises any one or combination of hydroxyethyl methacrylate, bisphenylglycidyl dimethacrylate, triethylene glycol dimethacrylate, other methacrylate-based and urethane-based polymers. 
     
     
         10 . The composite material of  claim 1 , wherein the composite material is modified by the attachment of an organic molecule, polymer, molecular machine, surface group or metal oxide to its surface. 
     
     
         11 . The composite material of  claim 1 , wherein the composite material is modified by the attachment of a fluorinated silane. 
     
     
         12 . The composite material of  claim 1  wherein the metal oxide structure is spherical. 
     
     
         13 . The composite material of  claim 1  wherein the metal oxide structure comprises silicon dioxide. 
     
     
         14 . A composite material comprising,
 a methacrylate-based or urethane-based resin; and,   a particulate filler dispersed in the resin,   wherein the particulate filler comprises a metal oxide structure containing a network of pores, said pores containing an antimicrobial active agent,   wherein the active agent has amphiphilic characteristics resulting in micellization when placed in aqueous conditions.   
     
     
         15 . The composite material of  claim 14  wherein the resin comprises a methacrylate-based resin. 
     
     
         16 . The composite material of  claim 14  wherein the resin comprises one or more of hydroxyethyl methacrylate, bisphenylglycidyl dimethacrylate and triethylene glycol dimethacrylate. 
     
     
         17 . The composite material of  claim 14  wherein the active agent comprises octenidine dihydrochloride, polyhexamethylene biguanide, cetylpyridinium chloride or lauric arginate. 
     
     
         18 . The composite material of  claim 14  wherein the active agent comprises octenidine or a salt thereof such as octenidine dihydrochloride. 
     
     
         19 . The composite material of  claim 14  wherein the metal oxide structure comprises silicon dioxide. 
     
     
         20 . The composite material of  claim 14  formulated as any one or more of, or as a component of: a coating for orthopedic implants, a resin tooth bonding agent, a cavity liner, a cavity varnish, a dental cement, a resin coating or bulk of dentures, a coating material or bulk of resin fillings, a coating material for endosseous dental implant abutment or component, a coating material for endosseous dental implant, a resin composite tooth restorative material, a denture relining, repairing, or rebasing resin, a pit and fissure sealant or conditioner, a temporary, interim or provisional crown or bridge resin, a root canal filling resin sealer or endodontic core material, a bone grafting material, a coating material for total temporomandibular joint prosthesis, a coating material for glenoid fossa prosthesis, a coating material for mandibular condyle prosthesis, a coating material for interarticular disc prosthesis, a coating material for orthodontic appliance, a resin bonding agent/cement for orthodontic brackets, a coating material or bulk of orthodontic plastic bracket, an oral cavity abrasive polishing agent, a dentifrice, a dental floss, and a massaging pick or tip for oral hygiene.