Coating for intraluminal expandable catheter providing contact transfer of drug micro-reservoirs

Abstract

A coating for an expandable portion of a catheter comprising a lipophilic matrix and a plurality of micro-reservoirs dispersed in the lipophilic matrix is disclosed. The plurality of micro-reservoirs comprises an active agent. A coating formulation and a method for forming the coating are also disclosed. A catheter comprising the coating on the expandable portion and a method for treating a condition are also provided.

1 . (canceled) 
     
     
         2 . A catheter comprising:
 an expandable portion on an elongated body; and   a coating over an outer surface of the expandable portion, wherein the coating comprises:
 a lipophilic matrix, wherein the lipophilic matrix comprises a fatty acid; 
 a plurality of micro-reservoirs dispersed in the lipophilic matrix, wherein the plurality of micro-reservoirs comprises an active agent; and 
 wherein the lipophilic matrix is configured to adhere to a luminal surface when the expandable portion is expanded, and transfer at least a portion of the plurality of micro-reservoirs to the luminal surface. 
   
     
     
         3 . The catheter of  claim 2 , wherein the active agent is crystalline. 
     
     
         4 . The catheter of  claim 2 , wherein the plurality of micro-reservoirs further comprises a biodegradable or bioerodable polymer. 
     
     
         5 . The catheter of  claim 4 , wherein the biodegradable or bioerodable polymer is selected from the group consisting of polylactic acid, polyglycolic acid and their copolymers, polydioxanone, polycarpolactone, polyphosphazine, collagen, gelatin, chitosan, and glycosoaminoglycans. 
     
     
         6 . The catheter of  claim 4 , wherein the active agent is about 10% to about 50% by weight of the micro-reservoirs. 
     
     
         7 . The catheter of  claim 2 , wherein the lipophilic matrix comprises the fatty acid and a cholesterol. 
     
     
         8 . The catheter of  claim 7 , wherein the weight ratio of the cholesterol to the fatty acid is in the range of about 1:2 to about 3:1, about 1:15 to about 2.5:1, or about 1:1 to about 2.1. 
     
     
         9 . The catheter of  claim 2 , wherein the fatty acids are found in serum or cell membranes. 
     
     
         10 . The catheter of  claim 2 , wherein the fatty acid is selected from the group consisting of lauric acid, lauroleic acid, tetradeadienoic acid, octanoic acid, myristic acid, myristoleic acid, decenoic acid, decanoic acid, hexadecenoic acid, palmitoleic acid, palmitic acid, linolenic acid, linoleic acid, oleic acid, vaccenic acid, stearic acid, eicosapentaenoic acid, arachadonic acid, mead acid, arachidic acid, docosahexaenoic acid, docosapentaenoic acid, docosatetraenoic acid, docosenoic acid, tetracosanoic acid, hexacosenoic acid, pristanic acid, phytanic acid, and nervonic acid. 
     
     
         11 . The catheter of  claim 2 , wherein the lipophilic matrix further comprises a sterol. 
     
     
         12 . The catheter of  claim 11 , wherein the sterol is selected from the group consisting of cholesterol, stigmasterol, lanosterol, sitosterol, DHEA, N4-Cholesteryl-Spermine, Guanidium-Cholesterol/BGTC, and DC-Cholesterol. 
     
     
         13 . The catheter of  claim 2 , wherein the coating has a melting point between room temperature and body temperature. 
     
     
         14 . The catheter of  claim 2 , wherein the coating comprises about 10% to about 75% by weight of the plurality of micro-reservoirs. 
     
     
         15 . The catheter of  claim 2 , wherein the plurality of micro-reservoirs has an average diameter of about 1.5 microns to about 8 microns. 
     
     
         16 . The catheter of  claim 2 , wherein the plurality of micro-reservoirs has an average diameter of about 2.0 microns to about 6 microns. 
     
     
         17 . The catheter of  claim 2 , wherein the active agent is selected from the group consisting of paclitaxel, sirolimus, paclitaxel derivative, sirolimus derivative, paclitaxel analogues, sirolimus analogues, inhibitory RNA, inhibitory DNA, steroids, and complement inhibitors. 
     
     
         18 . The catheter of  claim 2 , wherein the coating further comprising a polyethylene glycol-lipid (PEG-lipid). 
     
     
         19 . The catheter of  claim 18 , wherein the PEG-lipid is selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-350 (DSPE-mPEG350), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-methoxy(polyethylene glycol)-350 (DPPE-mPEG350), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-350 (DOPE-mPEG350), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-550 (DSPE-mPEG550), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-550 (DPPE-mPEG550), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol)-500 (DOPE-mPEG550). 
     
     
         20 . The catheter of  claim 18 , wherein the PEG-lipid is about 1% to about 10% by weight of the hydrophobic matrix. 
     
     
         21 . The catheter of  claim 2 , wherein the coating further comprising one or more additives independently selected from penetrating enhancers and stabilizers. 
     
     
         22 . The catheter of  claim 2 , wherein the coating has a surface concentration of about 1 μg/mm 2  to about 10 μg/mm 2 . 
     
     
         23 . A catheter comprising:
 an expandable portion on an elongated body;   a coating of  claim 2  over the expandable portion; and   a release layer between the expandable portion and the coating, wherein the release layer is configured to release the coating from the expandable portion.   
     
     
         24 . The catheter of  claim 23 , wherein the release layer comprises DSPE-mPEG350 or DSPE-mPEG500. 
     
     
         25 . The catheter of  claim 23 , wherein the release layer has a surface concentration of about 0.1 μg/mm 2  to about 5 μg/mm 2 . 
     
     
         26 . The catheter of  claim 23 , further comprising a protective coating over the first coating. 
     
     
         27 . The catheter of  claim 26 , wherein the protective coating comprises a hydrophilic polymer, a carbohydrate, or an amphiphilic polymer. 
     
     
         28 . The catheter of  claim 26 , wherein the protective coating is a glycosaminoglycan or a crystalized sugar. 
     
     
         29 . The catheter of  claim 26 , wherein the protective coating has a surface concentration of about 0.1 μg/mm 2  to about 5 μg/mm 2 .