Balloon Catheter Systems for Delivery of Dry Drug Delivery Vesicles to a Vessel in the Body

Abstract

Devices and methods for balloon delivery of rapamycin and other hydrophobic compounds to the wall of blood vessels. Balloon catheters, such as those used for balloon angioplasty, are modified with the addition of a reservoir of dry micelles. The micelle preparation is reconstituted and the micelles are mobilized when the aqueous solution used to inflate the balloons is injected into the catheter. The micelles are infused into tissue surrounding the balloon when pressurized fluid within the balloon leaks through the wall of the balloon.

We claim: 
     
         1 . A method for delivery of drugs or therapeutic agents to a vessel within a body of a patient, said method comprising the steps of:
 providing a catheter system comprising:   a balloon catheter comprising a catheter body with a distal end adapted for insertion into vasculature of a patient, a porous balloon disposed on the distal end, a proximal end adapted for connection to a fluid source, and a lumen extending from the proximal end to the balloon;   a storage chamber with a reservoir of dry drug delivery vesicles;   reconstituting the drug delivery vessels in the storage chamber to create a suspension of reconstituted drug delivery vesicles of a size;   wherein the porous balloon has pores of predetermined size; and   the predetermined size of the pores is 2.5 to 125 times the size of the reconstituted drug delivery vesicles; and   forcing the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon and into body tissue surrounding the balloon.   
     
     
         2 . A method for delivery of drugs or therapeutic agents to a vessel within a body of a patient, said method comprising the steps of:
 providing a catheter system comprising:   a balloon catheter comprising a catheter body with a distal end adapted for insertion into vasculature of a patient, a porous balloon disposed on the distal end, a proximal end adapted for connection to a fluid source, and a lumen extending from the proximal end to the balloon;   a storage chamber with a reservoir of dry drug delivery vesicles;   reconstituting the drug delivery vessels in the storage chamber to create a suspension of reconstituted drug delivery vesicles of a size;   wherein the porous balloon has pores of predetermined size; and   the predetermined size of the pores is 2 to 50 times the size of the reconstituted drug delivery vesicles; and   forcing the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon and into body tissue surrounding the balloon.   
     
     
         3 . The method of  claim 1 , wherein the drug delivery vesicles comprise micelles loaded with rapamycin or rapamycin analogs. 
     
     
         4 . The method of  claim 1 , wherein the drug delivery vesicles comprise micelles loaded with ABT-578, zotarolimus, everolimus, biolimus A9, deforolimus, temsirolimus, tacrolimus, pimcrolimus, nitric oxide synthase, C3 exoenzyme, RhoA inhibitors, tubulusin, A3 agonists, CB2 agonists, 17-AAG, Hsp90 antagonists, tyrphostins, cathepsin S inhibitors, paclitaxel, dexamethasone, ceramides, dimethyl sphingosine, ether-linked diglycerides, ether-linked phosphatidic acids, sphinganines, estrogens, taxol, taxol analogs, actinomycin D, prostaglandins, vitamin A, probucol, Batimastat, Statins, Trapidil, mitomycin C or Cytochalasin B. 
     
     
         5 . The method of  claim 2 , wherein the drug delivery vesicles comprise micelles loaded with rapamycin or rapamycin analogs. 
     
     
         6 . The method of  claim 2 , wherein the drug delivery vesicles comprise micelles loaded with ABT-578, zotarolimus, everolimus, biolimus A9, deforolimus, temsirolimus, tacrolimus, pimcrolimus, nitric oxide synthase, C3 exoenzyme, RhoA inhibitors, tubulusin, A3 agonists, CB2 agonists, 17-AAG, Hsp90 antagonists, tyrphostins, cathepsin S inhibitors, paclitaxel, dexamethasone, ceramides, dimethyl sphingosine, ether-linked diglycerides, ether-linked phosphatidic acids, sphinganines, estrogens, taxol, taxol analogs, actinomycin D, prostaglandins, vitamin A, probucol, Batimastat, Statins, Trapidil, mitomycin C or Cytochalasin B. 
     
     
         7 . The method of  claim 1  wherein:
 the step of forcing the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon and into body tissue surrounding the balloon comprises injecting the suspension of reconstituted drug delivery vesicles into the balloon and pressurizing the balloon to a pressure of 6 to 12 atmospheres. 
 
     
     
         8 . The method of  claim 1  further comprising:
 performing the step of the forcing the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon and into body tissue surrounding the balloon to delivering the suspension of reconstituted drug delivery vesicles through the porous wall portion of the balloon into the blood vessel at a rate of 0.002 mL/second to 1. mL/second. 
 
     
     
         9 . The method of  claim 2  wherein:
 the step of forcing the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon and into body tissue surrounding the balloon comprises injecting the suspension of reconstituted drug delivery vesicles into the balloon and pressurizing the balloon to a pressure of 6 to 12 atmospheres. 
 
     
     
         10 . The method of  claim 2  further comprising:
 performing the step of the forcing the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon and into body tissue surrounding the balloon to delivering the suspension of reconstituted drug delivery vesicles through the porous wall portion of the balloon into the blood vessel at a rate of 0.002 mL/second to 1. mL/second. 
 
     
     
         11 . A catheter system comprising:
 a balloon catheter comprising a catheter body with a distal end adapted for insertion into vasculature of a patient, a porous balloon disposed on the distal end, a proximal end adapted for connection to a suspension chamber, and a lumen extending from the proximal end to the balloon;   a suspension of reconstituted drug delivery vessels disposed within the suspension chamber, with the suspension chamber in fluid communication with the balloon;   an inflator operably connected to the suspension chamber and the balloon; wherein the porous balloon has pores of predetermined size; and the predetermined size of the holes is 2.5 to 125 times the size of the reconstituted drug delivery vesicles; and   the inflator is operable to force the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon.   
     
     
         12 . A catheter system comprising:
 a balloon catheter comprising a catheter body with a distal end adapted for insertion into vasculature of a patient, a porous balloon disposed on the distal end, a proximal end adapted for connection to a suspension chamber, and a lumen extending from the proximal end to the balloon;   a suspension of reconstituted drug delivery vessels disposed within the suspension chamber, with the suspension chamber in fluid communication with the balloon;   an inflator operably connected to the suspension chamber and the balloon; wherein the porous balloon has pores of predetermined size; and wherein the porous balloon has pores of predetermined size; and the predetermines size of the holes is 2 to 50 times the size of the reconstituted drug delivery vesicles; and   the inflator is operable to force the suspension of reconstituted drug delivery vesicles through the lumen of the catheter and the porous balloon.   
     
     
         13 . The catheter system of  claim 11 , wherein the drug delivery vesicles comprise micelles loaded with rapamycin or rapamycin analogs. 
     
     
         14 . The catheter system of  claim 11 , wherein the drug delivery vesicles comprise micelles loaded with ABT-578, zotarolimus, everolimus, biolimus A9, deforolimus, temsirolimus, tacrolimus, pimcrolimus, nitric oxide synthase, C3 exoenzyme, RhoA inhibitors, tubulusin, A3 agonists, CB2 agonists, 17-AAG, Hsp90 antagonists, tyrphostins, cathepsin S inhibitors, paclitaxel, dexamethasone, ceramides, dimethyl sphingosine, ether-linked diglycerides, etherlinked phosphatidic acids, sphinganines, estrogens, taxol, taxol analogs, actinomycin D, prostaglandins, vitamin A, probucol, Batimastat, Statins, Trapidil, mitomycin C or Cytochalasin B. 
     
     
         15 . The catheter system of  claim 12 , wherein the drug delivery vesicles comprise micelles loaded with rapamycin or rapamycin analogs. 
     
     
         16 . The catheter system of  claim 12 , wherein the drug delivery vesicles comprise micelles loaded with ABT-578, zotarolimus, everolimus, biolimus A9, deforolimus, temsirolimus, tacrolimus, pimcrolimus, nitric oxide synthase, C3 exoenzyme, RhoA inhibitors, tubulusin, A3 agonists, CB2 agonists, 17-AAG, Hsp90 antagonists, tyrphostins, cathepsin S inhibitors, paclitaxel, dexamethasone, ceramides, dimethyl sphingosine, ether-linked diglycerides, etherlinked phosphatidic acids, sphinganines, estrogens, taxol, taxol analogs, actinomycin D, prostaglandins, vitamin A, probucol, Batimastat, Statins, Trapidil, mitomycin C or Cytochalasin B.