Versatile nanoparticulate biomaterial for controlled delivery and/or containment of therapeutic and diagnostic material

Abstract

The invention provides compositions for controlled delivery and/or containment of therapeutic and/or diagnostic agents comprising the agent or agents encapsulated by a matrix containing chitosan, polyethylene glycol (PEG) and/or polyvinyl alcohol (PVA), and tetra-methoxy-ortho-silicate (TMOS) or tetra-ethoxy-ortho-silicate (TEOS), as well as methods for preparing the compositions, and uses of the compositions for therapy and imaging.

1 . A composition for controlled delivery and/or containment of one or a combination of therapeutic and/or diagnostic agents comprising the agent or agents encapsulated in a matrix comprising a) chitosan, b) polyethylene glycol (PEG) and/or polyvinyl alcohol (PVA), and c) tetra-methoxy-ortho-silicate (TMOS) or tetra-ethoxy-ortho-silicate (TEOS). 
     
     
         2 . The composition of  claim 1 , wherein the polyethylene glycol has a molecular weight of 200 to 20,000 Daltons. 
     
     
         3 . The composition of  claim 1 , comprising a silane in addition to TMOS or TEOS. 
     
     
         4 . The composition of  claim 3 , wherein the additional silane contains an alkyl side chain, a PEG having a molecular weight of 200 to 400 Daltons, a sugar, an amino terminus, or a reactive sulfhydryl or carboxyl group. 
     
     
         5 . The composition of  claim 3 , wherein the additional silane is a hydrophobic silane. 
     
     
         6 . (canceled) 
     
     
         7 . The composition of  claim 1  comprising polyethylene glycol (PEG) and tetra-methoxy-ortho-silicate (TMOS). 
     
     
         8 . The composition of  claim 1 , wherein the composition is in the form of particles having a diameter of 10 nm to 1 μm. 
     
     
         9 . (canceled) 
     
     
         10 . The composition of  claim 1 , wherein the agent is one or more of a therapeutic peptide, a chemotherapeutic agent, melanin, an agent for treating erectile dysfunction or a urological disorder, a plasmid, an antioxidant, an anti-inflammatory agent, a radioprotectant, an antimicrobial agent, nitric oxide, growth hormone, a growth factor or a cytokine. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . The composition of  claim 1  comprising a fluorescent label or a radioactive label or an imaging agent. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . A method for preparing a composition for controlled delivery and/or containment of one or more therapeutic and/or diagnostic agent, the method comprising:
 (a) admixing the agent or agents with i) chitosan, ii) polyethylene glycol (PEG) and/or polyvinyl alcohol (PVA), and iii) tetra-methoxy-ortho-silicate (TMOS) or tetra-ethoxy-ortho-silicate (TEOS) in a buffered solution;   (b) drying the mixture of step (a) to produce a gel; and   (c) heating the gel to produce a glassy material, or lyophilizing the gel to produce a particulate material.   
     
     
         17 . The method of  claim 16 , wherein the polyethylene glycol has a molecular weight of 200 to 20,000 Daltons. 
     
     
         18 . The method of  claim 17 , where the TMOS or TEOS is diluted with an additional silane. 
     
     
         19 - 21 . (canceled) 
     
     
         22 . The method of  claim 16 , wherein the gel is heated in step (c) at a temperature of 70° C. or less than 70° C. 
     
     
         23 . The method of  claim 16 , which further comprises grinding or milling the material of step (c) to produce particles of a desired size. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . A composition produced by the method of  claim 16 . 
     
     
         28 . A method of treating a subject comprising administering a therapeutic amount of the composition of  claim 1  to the subject. 
     
     
         29 . The method of  claim 28 , wherein the subject has cancer or erectile dysfunction or is at risk for exposure to ionizing radiation. 
     
     
         30 - 32 . (canceled) 
     
     
         33 . A method of imaging a subject comprising administering the composition of  claim 1  to the subject. 
     
     
         34 - 36 . (canceled) 
     
     
         37 . A method of treating a subject with tissue damage, comprising: a) incorporating the composition of  claim 10  into stem cells, wherein the composition is in the form of nanoparticles and the nanoparticles comprise a therapeutic agent; and
 b) administering the stem cells of step a) to the subject in an amount and manner effective to treat tissue damage in the subject. 
 
     
     
         38 - 39 . (canceled) 
     
     
         40 . A method of evaluating distribution and retention of stem cells in a subject, comprising:
 a) incorporating the composition of  claim 13  into stem cells, wherein the composition is in the form of nanoparticles and the nanoparticles comprise an imaging agent;   b) administering the stem cells of step a) to the subject; and   c) imaging the subject over time to evaluate the distribution and retention of the stem cells in the subject.   
     
     
         41 - 44 . (canceled)