Sustained-release drug carrier composition

Abstract

The present invention provides compositions for extended release of an active ingredient, comprising a lipid-saturated matrix formed from a biodegradable polymer. The present invention also provides methods of producing the matrix compositions and methods for using the matrix compositions to provide controlled release of an active ingredient in the body of a subject in need thereof.

1 - 74 . (canceled) 
     
     
         75 . A substrate having its surface coated fully or partially with a biodegradable matrix composition, the matrix composition comprising:
 a. a polyester;   b. a first lipid comprising cholesterol;   c. a second lipid comprising at least one phospholipid selected from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC); and   d. a pharmaceutical active agent;   wherein the matrix has a multilayered structure in which the polyester and lipids are ordered in the form of layers, and when maintained in an aqueous environment provides sustained release of the pharmaceutical active agent.   
     
     
         76 . The coated substrate of  claim 75 , wherein the substrate comprises tricalcium phosphate (TCP) particles. 
     
     
         77 . The coated substrate of  claim 76 , wherein said TCP comprises β-tri calcium phosphate (β-TCP). 
     
     
         78 . The coated substrate of  claim 75  wherein the polyester is selected from the group consisting of PLA (polylactic acid), PGA (poly glycolic acid) and PLGA (Poly (lactic co glycolic acid). 
     
     
         79 . The coated substrate of  claim 75  wherein the pharmaceutical active agent is selected from an antibiotic, an antifungal, a non-steroidal anti-inflammatory drug, a steroid, an anti-cancer agent, an osteogenic factor and a bone resorption inhibitor. 
     
     
         80 . The coated substrate of  claim 79 , wherein said pharmaceutical active agent is an antibiotic or antifungal. 
     
     
         81 . The coated substrate of  claim 80 , wherein the antibiotic is doxycycline or doxycycline hyclate. 
     
     
         82 . The coated substrate of  claim 80 , wherein said pharmaceutical active agent is an anticancer agent. 
     
     
         83 . The coated substrate of  claim 80 , wherein said pharmaceutical active agent is a non-steroidal anti-inflammatory drug (NSAID). 
     
     
         84 . The coated substrate of  claim 79 , wherein said pharmaceutical active agent is a steroid. 
     
     
         85 . The coated substrate of  claim 84 , wherein said steroid is dexamethasone or dexamethasone 21-phosphate. 
     
     
         86 . The coated substrate of  claim 79 , wherein said pharmaceutical active agent is selected from an osteogenic factor or a bone resorption inhibitor. 
     
     
         87 . The coated substrate of  claim 75 , wherein the weight ratio of total lipids to said biodegradable polyester is between 1.5:1 and 9:1 inclusive. 
     
     
         88 . The coated substrate of  claim 75 , comprising a plurality of pharmaceutical active agents selected from an antibiotic, an antifungal, a non-steroidal anti-inflammatory drug (NSAID), a steroid, an anti-cancer agent, an osteogenic factor and a bone resorption inhibitor. 
     
     
         89 . The coated substrate of  claim 75 , wherein said matrix composition is homogeneous. 
     
     
         90 . The coated substrate of  claim 75 , wherein the matrix composition further comprises at least one of a sphingolipid, a tocopherol, an additional phospholipid selected from the group consisting of a phosphatidylserine, a phosphatidylglycerol, and a phosphatidylinositol, a free fatty acid having 14 or more carbon atoms, a PEGylated lipid and a targeting moiety capable of interacting with a target molecule selected from the group consisting of a collagen molecule, a fibrin molecule and a heparin. 
     
     
         91 . The coated substrate of  claim 75 , wherein said cholesterol is present in an amount of 5-50 mole percent of the total lipid content of said matrix composition. 
     
     
         92 . The coated substrate of  claim 75 , wherein said matrix composition is substantially devoid of water. 
     
     
         93 . The coated substrate of  claim 75  for the sustained release of said pharmaceutical active agent, wherein at least 50% of said pharmaceutical active agent is released from the composition at zero-order kinetics. 
     
     
         94 . A pharmaceutical composition comprising the coated substrate of  claim 75 , for sustained release of the pharmaceutically active agent.