Natural biodegradable matrices and uses thereof

Abstract

Matrices formed from a natural biodegradable material and that exhibit surface degradation in the presence of an enzyme are described. Matrices including a bioactive agent can be implanted or formed in a subject for release of the bioactive agent upon degradation of the matrix. The matrix can be provided in various forms, including coatings for implantable devices, implants, and in-situ formed matrices. The matrix can also be in the form of a medical device having a structure that is used to treat a medical condition.

1 . A method of delivering a bioactive agent to a subject comprising the steps of:
 providing a matrix of natural biodegradable material comprising bioactive agent entrapped within the matrix, wherein the matrix has a surface, and wherein the matrix is implanted or immobilized within the subject; and   allowing the surface to be contacted with an enzyme, wherein the matrix prevents the enzyme from entering the matrix, wherein the enzyme degrades the matrix at the surface, and wherein bioactive agent is released from the matrix upon degradation of the natural biodegradable material.   
   
   
       2 . The method of  claim 1 , wherein the matrix is in the form of a coating on an implantable medical article. 
   
   
       3 . The method of  claim 1 , wherein the matrix is in the form of an in situ-formed hydrogel. 
   
   
       4 . The method of  claim 1 , wherein the matrix is in the form of an implantable device. 
   
   
       5 . The method of  claim 1 , wherein the natural biodegradable material comprises a natural biodegradable polymer. 
   
   
       6 . The method of  claim 5 , wherein the natural biodegradable material comprises a natural biodegradable polysaccharide. 
   
   
       7 . The method of  claim 6 , wherein the natural biodegradable polysaccharide is selected from the group consisting of maltodextrin, polyalditol, and amylose. 
   
   
       8 . The method of  claim 1 , wherein the matrix is formed of cross-linked natural biodegradable polymers. 
   
   
       9 . The method of  claim 1 , wherein the natural biodegradable material has a molecular weight of less than 100,000 Da. 
   
   
       10 . The method of  claim 1 , wherein the natural biodegradable material has a molecular weight of less than 50,000 Da. 
   
   
       11 . The method of  claim 1 , wherein the natural biodegradable material has a molecular weight in the range of 1000 Da to 10,000 Da. 
   
   
       12 . The method of  claim 1 , wherein the step of allowing, the enzyme is a carbohydrase. 
   
   
       13 . The method of  claim 12 , wherein the step of allowing, the enzyme is α-amylase. 
   
   
       14 . The method of  claim 1  wherein the bioactive agent is selected from the group consisting of polypeptides, polynucleotide, polysaccharides, viral particles, and cells. 
   
   
       15 - 20 . (canceled) 
   
   
       21 . The method of  claim 1 , wherein the natural biodegradable material has a molecular weight of less than 500,000 Da. 
   
   
       22 . The method of  claim 1 , wherein the natural biodegradable material has a molecular weight of less than 250,000 Da. 
   
   
       23 . The method of  claim 1 , wherein the matrix is formed from a composition comprising natural biodegradable polymers comprising pendent polymerizable groups. 
   
   
       24 . The method of  claim 23 , wherein the pendent polymerizable groups are selected from the group consisting of vinyl groups, acrylate groups, methacrylate groups, ethacrylate groups, 2-phenyl acrylate groups, acrylamide groups, methacrylamide groups, itaconate groups, and styrene groups. 
   
   
       25 . The method of  claim 1 , wherein the matrix is formed from a composition comprising natural biodegradable polymers at a concentration in the range of 5-50% (w/v). 
   
   
       26 . The method of  claim 25 , wherein the matrix is formed from a composition comprising natural biodegradable polymers at a concentration in the range of 20-50% (w/v).