Patent Publication Number: US-2007112330-A1

Title: Therapeutic delivery balloon

Description:
RELATED APPLICATION  
      This application is a continuation of U.S. application Ser. No. 09/760,807, which was filed on Jan. 17, 2001, is entitled “Therapeutic Delivery Balloon,” and is incorporated herein in its entirety. 
    
    
     TECHNICAL FIELD  
      The present invention regards the delivery of therapeutic to a target site of an organic vessel. More particularly the present invention regards the delivery of therapeutic to the interior walls of a lumen via a hyper-deformable inflatable balloon placed within the lumen.  
     BACKGROUND OF THE INVENTION  
      The delivery of therapeutic to the interior lumen walls of a diseased vessel is an important, often repeated, procedure in the practice of modem medicine. The delivery of the therapeutic can be completed through the use of numerous devices and procedures including direct injection by syringe and needle, pneumatic injection of the therapeutic into the diseased tissue, and the release of the therapeutic, near the target site, by the distal end of a catheter inserted into the lumen. When the diseased or otherwise targeted area is irregularly shaped its unorthodox shape can retard the effective and uniform delivery and absorption of the therapeutic at the target site. For example, as can be seen in  FIG. 1 , which depicts a drug delivery bladder  13  being used to place therapeutic against the interior walls of lumen  12  in vessel  10 , the walls of the bladder  13  do not touch all of the walls of the lumen  12 . As can be seen the vessel  10  contains a calcification  11  that acts to distort the configuration of lumen  12 . Previously round, the lumen  12  has been distorted into a reniform configuration due to the disforming forces of the calcification  11 . Accordingly, when the bladder  13 , located on the distal end of a catheter  14  is inflated, only a portion of the bladder&#39;s  13  exterior surface comes in contact with the interior wall of the lumen  12  and, thus, only this contacted portion can be directly reached by the therapeutic. Likewise, when the wall of the lumen  12  has a cratered or otherwise irregular profile, which is typical in arteries inflicted with arteriosclerosis, the expanding bladder is unable to contact the entire surface area of the wall of the lumen  12 . When this occurs, therapeutic being delivered is sporadically and unevenly placed at the target site, leaving portions of the lumen wall unexposed to the therapeutic.  FIG. 1   a  provides an illustrative enlarged example of an interface between a bladder surface  15  and an irregularly shaped lumen wall  16 . As is evident, certain craters  17  of the lumen wall  16  are not in contact with the bladder surface  15 . Therefore, irregularly shaped lumen walls present an impediment to and a retarding factor in the delivery of therapeutic to the irregularly shaped lumen walls.  
     SUMMARY OF THE INVENTION  
      The present invention regards a therapeutic delivery balloon. In one embodiment a system for delivering therapeutic to an irregular interior vessel surface is provided. This system includes a catheter having a proximal end, a distal end, and an internal lumen; a source of fluid in communication with the internal lumen of the catheter; and, a first inflatable balloon having an exterior surface, wherein the balloon is hyper-deformable, is in communication with the internal lumen of the catheter, and has an exterior surface in communication with a therapeutic when the balloon is in an expanded state.  
      In an alternative embodiment of the present invention a method for delivering therapeutic to an irregular interior vessel surface of a patient is provided. This method includes: inserting an expandable hyper-deformable membrane into the vessel of the patient, the expandable hyper-deformable membrane having an exterior surface; positioning the expandable hyper-deformable membrane at an irregular interior surface of the vessel within the patient; and, forcing fluid into the expandable hyper-deformable membrane to expand the expandable hyper-deformable membrane, the expandable hyper-deformable membrane becoming juxtaposed to the irregular interior surface of the vessel of the patient. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1  is a cross-sectional view of an expandable bladder located within an irregularly shaped lumen of a vessel.  
       FIG. 1   a  is an enlarged cross-sectional view of an interface point between an expandable bladder and an irregularly shaped lumen wall.  
       FIG. 2  is a cross-sectional view of an expanded hyper-deformable inflatable balloon within an irregularly shaped lumen of a vessel in accordance with an embodiment of the present invention.  
       FIG. 2   a  is an enlarged cross-sectional view of a portion of a hyper-deformable inflatable balloon conforming to an irregularly shaped lumen wall in accordance with an alternative embodiment of the present invention.  
       FIG. 3  is a cross-sectional view, with an enlarged portion, of a distal end of a catheter employing a hyper-deformable inflatable balloon as employed within an irregularly shaped lumen in accordance with another alternative embodiment of the present invention.  
       FIG. 4  is a side view of a distal end of a catheter employing a hyper-deformable inflatable balloon in accordance with another alternative embodiment of the present invention.  
       FIG. 5  is a side view of the hyper-deformable inflatable balloon of  FIG. 4  in an inflated configuration.  
       FIG. 6  is a side view of a catheter employing a dilating bladder and a hyper-deformable inflatable balloon in accordance with another alternative embodiment of the present invention.  
       FIG. 7  is a sectional view taken along line  7 - 7  of  FIG. 6 .  
       FIG. 8  is a side view of the distal end of a catheter located near an irregular surface of a lumen in accordance with another alternative embodiment of the present invention.  
       FIG. 9  is a side view of the distal end of the catheter from  FIG. 8  illustrating the dilation bladder and the hyper-deformable balloon in an expanded state.  
       FIG. 10  is a side view of the distal end of the catheter from  FIG. 8  after the dilation bladder and hyper-deformable balloon illustrated in  FIG. 9  have been deflated.  
       FIG. 11  is a side view of the distal end of the catheter from  FIG. 8  illustrating the hyper-deformable inflatable balloon in an inflated state.  
       FIG. 12  is a side view of the distal end of a catheter in accordance with another alternative embodiment of the present invention.  
       FIG. 13  is a side view of the catheter from  FIG. 12 .  
       FIG. 14  is a side view of the distal end of a catheter in accordance with another alternative embodiment of the present invention.  
       FIG. 15  is a side view of a catheter in accordance with another alternative embodiment of the present invention. 
    
    
     DETAILED DESCRIPTION  
       FIG. 2  is an enlarged cross-sectional view of a vessel  20 , having a lumen, located within the body of a patient. The vessel  20  contains reniform interior lumen wall surface  21 . As can be seen, this interior lumen wall surface  21  is shaped in an irregular configuration due to the calcification  24  located within the wall of the vessel  20 . This calcification  24  places pressure on the interior lumen wall surface  21 , causing it to deform into its irregular shape.  
      Also depicted in  FIG. 2  is a hyper-deformable inflatable balloon  22 . This balloon  22 , which is shown in its inflated state, is mounted on the distal end of catheter  28 . Positioned between the lumen wall surface  21  and the hyper-deformable inflatable balloon  22  is a therapeutic  23 . The therapeutic  23  may be used to treat, regenerate, or otherwise affect the interior lumen wall surface  21  or the vessel wall itself. The proximity of the hyper-deformable inflatable balloon  22 , the interior lumen wall surface  21 , and the therapeutic  23  is clearly shown in the enlarged portion of  FIG. 2 .  
      As can be seen in the enlarged portion of  FIG. 2 , the hyper-deformable inflatable balloon  22  closely mimics and contours to the interior lumen wall surface  21  such that the therapeutic  23  located on the exterior of the hyper-deformable inflatable balloon may be placed adjacent to and in contact with the interior lumen wall surface  21  by the exterior surface of the balloon  22 . The term hyper-deformable as used herein includes materials that are capable of stretching or expanding in order to closely replicate the irregular surfaces with which they are expanded up against. Due to the hyper-deformability of the inflatable balloon  22 , some areas of the balloon will stretch further from the catheter  28  than others. This is made evident in  FIG. 2 , which illustrates the varying distances from the catheter  28  that the balloon may travel.  
      The hyper-deformable inflatable balloon  22  may be made with any material that is hyper-deformable. Latex, silicone, polyurethane, rubber (including styrene and isobutylene styrene), and nylon, are each examples of materials that may be used in manufacturing the hyper-deformable balloon. Moreover, the actual configuration of the balloon may also make it hyper-deformable. For example, the balloon may be internally ribbed or notched or otherwise specifically configured to increase its deformability and, thus, make it readily conformable to its surroundings in an expanded state.  
      The vessel  20  may be any vessel located within or outside of the body of a patient. It may include blood-carrying vessels such as the veins, arteries, and chambers of the heart, it may also include the esophagus, the ureters, the intestines, the pockets of fluid located within the individual vertebrae of the spinal column and any other suitable vessel as apparent to one of skill in the art. Organs and tissues that may be treated by the methods of the present invention include any mammalian tissue or organ, whether located in vivo or ex vivo. Non-limiting examples include the heart, the lungs, the brain, the livers, the kidneys, the bladder, the intestines, the stomach, the pancreas, the ovaries, the prostate, the eyes, as well as tumors, cartilage and bone.  
       FIG. 2   a  is an enlarged sectional view of the interface point of an inflated hyper-deformable inflatable balloon  25  conforming to an irregular surface of a vessel wall  26 . As can be seen in  FIG. 2   a , the hyper-deformable inflatable balloon  25  has very closely conformed to the irregular surface of the vessel wall  26 . Because the hyper-deformable inflatable balloon  25  is able to conform to the irregular surface of the vessel wall  26 , the therapeutic  27 , previously located on the outside surface of the balloon  25 , may come in direct contact with the entire surface of the irregularly shaped vessel wall  26 .  
       FIG. 3  illustrates an enlarged sectional view of the distal end of a catheter  31  located within a vessel  30  having an irregularly shaped lumen wall  35 . The distal end of the catheter  31  is shown in  FIG. 3  as being inserted past the irregular shaped lumen wall  35 . As can be seen, the surface of the distal end of the catheter  31  contains a plurality of orifices  34  situated within and in fluid communication with the hyper-inflatable balloon  33 . These orifices, while round, may be any configuration that provides for the exit of the fluid from inside of the catheter  31  to inside of the balloon  33 . Also evident in this figure is a therapeutic  32 , which has been previously placed on the exterior surface of the hyper-deformable inflatable balloon  33 .  
      In use, bio-compatible non-compressible fluid will be pumped from the proximal end of the catheter  31  down a lumen in the catheter and out the orifices  34  of the catheter  31  to inflate the hyper-deformable inflatable balloon  33 . The balloon  33 , in this embodiment, inflates under the pressure of the fluid, being pumped out of the orifices  34 , until the balloon  33  comes in contact with the irregularly shaped lumen wall  35 . Due to the hyper-deformability of the balloon  33 , the balloon  33  is able to conform to the irregularly shaped lumen wall  35  and, therefore, expose the irregularly shaped lumen wall  35  to the therapeutic  32  located on the outside of the hyper-deformable inflatable balloon  33 .  
      The interface between the hyper-deformable inflatable balloon  33 , the therapeutic  32 , and the irregularly shaped lumen wall  35  is clearly shown in the enlarged circle of  FIG. 3 . As is evident in this embodiment, when the balloon  33  is inflated its hyper-deformability allows the therapeutic  32  to be placed adjacent to and in contact with the entire surface of the irregularly shaped lumen wall  35 .  
      While the orifices  34  in  FIG. 3  are illustrated as being evenly and uniformly spaced along the catheter  31 , these orifices  34  may be of different sizes or different shapes and may be located at different spacings along the catheter. In a preferred embodiment, however, these orifices will be evenly spaced along the catheter  31  to facilitate the even distribution of fluid into the hyper-deformable inflatable balloon and, consequently, the even and uniform inflation of the balloon  33 .  
      In this embodiment, the fluid may be pumped into the catheter through a syringe (which is illustrated in  FIGS. 4-6 ,  13 , and  15 ) located at the proximal end of the catheter or, alternatively, through any other pumping means that can apply a pressure on the fluid to carry it into the balloon. These alternative means could include a micro-pump, an inflator, and a collapsible bladder. In a preferred embodiment, the amount of fluid being injected into the catheter and/or the infusion pressure placed on the fluid, will be measured to help monitor the expansion of the balloon  33  within the vessel  30  and to preclude an overabundance of fluid from being injected into the balloon  33 , causing the balloon  33  or the vessel  30  to unwantedly rupture. By measuring the amount of pressure placed on the fluid the operator can monitor the progress of the procedure. In this preferred embodiment, the amount of pressure generated in the vessel will not exceed a known tolerable pressure level for the vessel being treated. Lastly, due to the risk of rupture, it is preferred that any fluid used to expand the hyper-deformable inflatable balloon  33  be bio-compatible with the environment in which the hyper-deformable inflatable balloon  33  and catheter  31  are employed. These fluids can include contrast solutions such as those used in ultrasound, fluoroscopy, and MRI procedures as well as various brine solutions.  
       FIG. 4  is a side view of a catheter  40  in accordance with another alternative embodiment of the present invention. The distal tip  48 , tube  42 , syringe  41 , plunger  46 , therapeutic  43 , and hyper-deformable inflatable balloon  44  of the catheter  40  are all clearly evident in  FIG. 4 . As can be seen and as discussed above, the syringe  41  has been attached to the proximal end of the catheter  40 . This syringe  41  may contain a fluid that is injected and pushed down through the tube  42  of the catheter  40 , by depressing the plunger  46 , to inflate the balloon  44 . Upon being inflated, therapeutic  43  may be placed adjacent to and in contact with an irregularly shaped lumen wall located near the distal end of the catheter  40 . In this embodiment the therapeutic has been placed on the surface of the balloon  44  prior to the commencement of the medical procedure. Alternatively, as discussed below, the therapeutic  43  may also be pumped to the surface of the balloon before or during the completion of the procedure.  
       FIG. 5  is a side view of the catheter from  FIG. 4 . As can be seen, the hyper-deformable inflatable balloon  44  is illustrated in an extended position. As is also evident, the plunger  46 , previously shown in an extended position in  FIG. 4 , is shown in a compressed position in  FIG. 5 . As a result of depressing or compressing the plunger  46  from the first position to the second position, the hyper-deformable inflatable balloon  44  has been inflated. It will be evident to one of skill in the art that  FIG. 5  is clearly not drawn to scale as the amount of fluid displaced by the movement of the plunger  46  would be smaller than the volume of the inflated balloon  44  illustrated in  FIG. 5 .  
      As mentioned above, the volume of fluid injected into the hyper-deformable inflatable balloon  44  may be measured and monitored during the procedure to control the rate and amount of balloon  44  inflation. This measurement may be completed by placing striations or markings along the side of the syringe  41  and then counting the number of markings that the plunger  46  has passed through. Alternatively, if another type of pump is used this pump may be calibrated to measure the amount of fluid injected into the lumen of the catheter, the amount of resistive force pushing back on fluid being pumped into the lumen or both. Moreover, the pump or any of the inflation devices, may be used to control the rate at which the balloon is expanded. Also, the tracing fluid described above, may be used in concert with an imaging device to track the progress of the expansion of the delivery balloon  44 .  
       FIG. 6  is a side view of another alternative embodiment of the present invention. In  FIG. 6 , a catheter  60  has a first syringe  64 , a second syringe  63 , and the end of guide wire  601  located at its proximal end and a hyper-deformable inflatable balloon  65  and a dilation bladder  66  located at its distal end. Also illustrated in  FIG. 6  are the catheter body  61 , the first lumen  62 , the second lumen  68 , orifices  67 , and openings  69 . The first syringe  64  may be in fluid communication with the first lumen  62  and the opening  69  in this embodiment. The second syringe  63  may be in fluid communication with the orifices  67  through the second lumen  68  in this embodiment. The first syringe  64  may be in fluid communication with the openings  69  through the first lumen  62  in this embodiment.  
      In use, when the distal end of the catheter  60  is placed within a lumen of the body through the use of the guide wire  601  the dilation bladder  66  may be inflated to first dilate the lumen and then, next, the hyper-deformable inflatable balloon  65  may be inflated to place therapeutic against the irregular but now dilated surface of the lumen. The openings  69  are located on the first lumen within the distillation bladder  66  such that when the first syringe  64  is depressed, fluid may be pumped into the dilation bladder  66  and the dilation bladder  66  will expand. Similarly, the orifices  67  may be located along the second lumen  68  and positioned such that when the second syringe  63  is depressed, the balloon  65  will be forced to expand.  
      As described above, fluid may be used to inflate both the bladder and the balloon, and the volume and rate of entry of this fluid may be monitored to help measure the progress of the procedure and to perform various maneuvers and steps of the delivery procedure.  
       FIG. 7  is a cross-sectional view taken along line  7 - 7  of  FIG. 6 . The first lumen  62 , the second lumen  68 , the openings  69 , the catheter body  61 , the dilation bladder  66 , the guide wire  601 , and the hyper-deformable inflatable balloon  65  are all clearly evident in this view. As can be seen, the openings  69  are evenly spaced along the catheter body  61 . In addition, while three openings  69  are shown in this embodiment, other configurations of the openings may be employed, including varying the number of openings and openings of different shapes and sizes.  
      The catheter body  61  in this embodiment, as well as in the other embodiments, may be made from numerous materials, including stainless steel, plastic, and other suitably rigid polymers. It is preferable that the materials used are compatible with the target sites in which they can be used and that they may be able to withstand the pressures generated by the fluids passing through them. In addition, they should be flexible enough such that the catheter may be effectively snaked down through a vessel in the body having an irregularly shaped lumen.  
       FIGS. 8-11  illustrate the various steps that may be employed in utilizing an alternative embodiment of the present invention. As can be seen in  FIG. 8 , the distal end of a catheter  82  has been inserted into a vessel  80 . This vessel  80  contains irregular lumen walls  81 . The arrow  85  in  FIG. 8  illustrates the direction in which the catheter  82  has been inserted into the vessel  80 . Also evident in  FIG. 8  are the balloon  83  and the dilation bladder  84 , both located at the distal end of the catheter  82 .  
      During an initial step illustrated in  FIG. 9 , the dilation bladder  84  may be inflated by injecting fluid down the catheter  82 , thereby enlarging the dilation bladder  84 . As can be seen, as the dilation bladder enlarges, so, too, does the balloon  83 , whereby both the enlarged balloon and the enlarged bladder swell to meet the irregular lumen wall  81 . Due to the structural rigidity of the bladder  84 , the previously narrow and highly irregular lumen wall  81  has been smoothed over and dilated by the forces exerted from the bladder  84  to the wall  81 . As can be seen in  FIG. 9 , due to the rigidity of the bladder  84 , spaces  91  exist between the balloon  83  and the irregular lumen wall  81  while the bladder  84  is in an expanded state. Also evident in  FIG. 9  are uncontacted areas  90  and voids  91  wherein the balloon  83  has not come in contact with the irregular lumen wall  81  at all.  
      These uncontacted areas  90  and voids  91  form, because the bladder  84 , used to dilate the vessel  80  and compact the irregular lumen walls  81 , is a rigid and partially flexible material. The material from which the bladder  84  is made may be non-compliant, semi-compliant or compliant but should be rigid enough such that when the dilating bladder  84  is inflated it may dilate the lumen in which it is placed.  
      In  FIG. 10 , the dilation bladder  84  has been shrunk by extracting the fluid used to expand it through a suction force generated at the proximal end of the catheter  82 . This suction force may be generated by pulling on a plunger attached to the syringe, through a vacuum pump located at the proximal end of the catheter  82  or through any other suitable means. As can be seen in  FIG. 10 , the balloon  83  did not contact the entire surface of the irregular lumen wall  81  as made evident by non-contact points  101  which are illustrated in this figure. Conversely, the balloon did contact some points of the lumen wall, these contact points  100  are identified in Fig.  10 . As suggested by their name, they indicate where the balloon  83  contacted the irregular lumen wall  81  during expansion of the bladder  84 .  
      In  FIG. 11 , the balloon  83  has been inflated through the injection of fluid down the catheter under a pressure generated in a pump or other inflation device located at the proximal end of the catheter (which is not shown). As can be seen in  FIG. 11 , the balloon  83 , which is hyper-deformable, has expanded and comes in complete contact with the irregularly shaped lumen wall  81  in this embodiment. This is advantageous because therapeutic  86  located on the outside surface of the balloon  83  may be maintained against the entire surface of the irregular lumen wall  81  while the balloon  83  remains in its expanded state.  
      With each of the previous embodiments, the therapeutic has been placed or coated on the exterior surface of the inflatable balloon. Alternatively, as suggested above and as described in the following embodiments, the therapeutic may also be located within the inflatable balloon and then forced out through the inflatable balloon to its exterior surface through orifices located in the inflatable balloon or, alternatively, through the balloon itself because the therapeutic may itself be permeable relative to the material comprising the balloon.  
       FIG. 12  illustrates the distal end of a catheter  120  in accordance with an alternative embodiment of the present invention. This catheter  120  has a first balloon  121  located at its distal end, the first balloon  121  contains a plurality of orifices  122 . As mentioned above and as described below, the therapeutic in this embodiment may be located within the first balloon  121  and may be squeezed to its surface after the balloon has been located at the target site within the lumen.  
       FIG. 13  is a side view of the catheter from  FIG. 12  showing the internal components of the balloon  121 . As can be seen, the balloon  121 , which contains a plurality of orifices  122 , also contains a second balloon  130  and a layer of therapeutic  131  positioned between the surface of the second balloon  130  and the balloon  121 .  
      In use, the embodiment illustrated in  FIGS. 12 and 13  may be inserted into an irregularly shaped lumen as described above. Then, as required, the second internal balloon  130  may be inflated, first forcing the first balloon  121  up against the lumen wall and then forcing the therapeutic  131  out through the orifices  122  such that the therapeutic  131  may come in contact with the entire surface of the irregularly shaped lumen wall. An advantage of this configuration is that the therapeutic is not located on the outside of the first balloon and, therefore, is less at risk of becoming errantly placed at a non-target area of the lumen as the catheter is positioned within the body. Alternatively, in another embodiment, rather than having the therapeutic resident on the surface of the inner second balloon, it may, instead, be pumped between the two balloons, from the catheter, during the performance of the procedure.  
      The embodiment illustrated in  FIG. 14  is similar to the alternative embodiments illustrated in  FIGS. 12 and 13 .  FIG. 14  illustrates the distal end of a catheter  143  in accordance with another alternative embodiment of the present invention. In the alternative embodiment of  FIG. 14 , rather than having orifices  122  described in the above embodiment, the balloon  141  is manufactured with a material that is permeable to the therapeutic  140  which is located between the second balloon  142  and the first balloon  141 . As the second balloon  142  is inflated and the first balloon  141  comes in contact with and rests up against the irregularly shaped lumen surface, the therapeutic  140 , resident between the two balloons, may be squeezed through the permeable membrane of the first balloon  141 , out onto the exterior surface of the balloon, and in contact with the irregularly shaped lumen wall.  
       FIG. 15  is a side view of a catheter in accordance with another alternative embodiment of the present invention. The catheter in this embodiment contains an exit orifice  152 , an entrance orifice  151 , a slide cover  153 , a pull ring  150 , and a string  154 . The exit orifice  152  and the entrance orifice  151  may be fluidly connected within the catheter by a channel or lumen. When the catheter in  FIG. 15  is used within an artery or vein of the body, and when the balloon has been inflated, thereby allowing therapeutic to be placed up against the wall of either of these lumens, the slide  153  may be slid open by pulling on the ring  150 —allowing blood to flow from the entrance orifice  151 , through the lumen within the catheter, and out the exit orifice  152 . By allowing blood to flow through the catheter as the catheter is applying therapeutic to the target area, the catheter may be retained in place for a longer period of time. This is especially preferred when the catheter is used in various procedures involving vessels located within the torso of a patient.  
      The term “therapeutic” as used throughout includes one or more “therapeutic agents” or “drugs.” The terms “therapeutic” and “drugs” are used interchangeably herein and include pharmaceutically active compounds, nucleic acids with and without carrier vectors such as lipids, compacting agents (such as histones), virus (such as adenovirus, andenoassociated virus, retrovirus, lentivirus and a-virus), polymers, hyaluronic acid, proteins, cells and the like, with or without targeting sequences. The therapeutics administered in accordance with the invention includes the therapeutic agent(s) and solutions thereof.  
      Specific examples of therapeutic agents used in conjunction with the present invention include, for example, pharmaceutically active compounds, proteins, cells, oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compacting agents, gene/vector systems (i.e., any vehicle that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector or in a viral vector and which further may have attached peptide targeting sequences; antisense nucleic acid (RNA or DNA); and DNA chimeras which include gene sequences and encoding for ferry proteins such as membrane translocating sequences (“MTS”) and herpes simplex virus-1 (“VP22”)), and viral, liposomes and cationic and anionic polymers and neutral polymers that are selected from a number of types depending on the desired application. Non-limiting examples of virus vectors or vectors derived from viral sources include adenoviral vectors, herpes simplex vectors, papilloma vectors, adeno-associated vectors, retroviral vectors, and the like. Non-limiting examples of biologically active solutes include anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPACK (dextrophenylalanine proline arginine chloromethylketone); antioxidants such as probucol and retinoic acid; angiogenic and anti-angiogenic agents and factors; agents blocking smooth muscle cell proliferation such as rapamycin, angiopeptin, and monoclonal antibodies capable of blocking smooth muscle cell proliferation; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine; calcium entry blockers such as verapamil, diltiazem and nifedipine; antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; antimicrobials such as triclosan, cephalosporins, aminoglycosides, and nitorfurantoin; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors such as lisidomine, molsidomine, L-arginine, NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NO adducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet factors; vascular cell growth promotors such as growth factors, growth factor receptor antagonists, transcriptional activators, and translational promotors; vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents; vasodilating agents; agents which interfere with endogeneus vascoactive mechanisms; survival genes which protect against cell death, such as anti-apoptotic Bcl-2 family factors and Akt kinase; and combinations thereof. Cells can be of human origin (autologous or allogenic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at the injection site. The delivery mediated is formulated as needed to maintain cell function and viability. Any modifications are routinely made by one skilled in the art.  
      Polynucleotide sequences useful in practice of the invention include DNA or RNA sequences having a therapeutic effect after being taken up by a cell. Examples of therapeutic polynucleotides include anti-sense DNA and RNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA to replace defective or deficient endogenous molecules. The polynucleotides of the invention can also code for therapeutic proteins or polypeptides. A polypeptide is understood to be any translation product of a polynucleotide regardless of size, and whether glycosylated or not. Therapeutic proteins and polypeptides include as a primary example, those proteins or polypeptides that can compensate for defective or deficient species in an animal, or those that act through toxic effects to limit or remove harmful cells from the body. In addition, the polypeptides or proteins that can be injected, or whose DNA can be incorporated, include without limitation, angiogenic factors and other molecules competent to induce angiogenesis, including acidic and basic fibroblast growth factors, vascular endothelial growth factor, hif-1, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin like growth factor; growth factors; cell cycle inhibitors including CDK inhibitors; anti-restenosis agents, including p15, p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase (“TK”) and combinations thereof and other agents useful for interfering with cell proliferation, including agents for treating malignancies; and combinations thereof. Still other useful factors, which can be provided as polypeptides or as DNA encoding these polypeptides, include monocyte chemoattractant protein (“MCP-1”), and the family of bone morphogenic proteins (“BMP&#39;s”). The known proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP- 7  (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP&#39;s are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the “hedgehog” proteins, or the DNA&#39;s encoding them.  
      The therapeutic and the delivery balloon may be used, for example, in any application for treating, preventing, or otherwise affecting the course of a disease or tissue or organ dysfunction. For example, the methods of the invention can be used to induce or inhibit angiogenesis, as desired, to prevent or treat restenosis, to treat a cardiomyopathy or other dysfunction of the heart, for treating Parkinson&#39;s disease or a stroke or other dysfunction of the brain, for treating cystic fibrosis or other dysfunction of the lung, for treating or inhibiting malignant cell proliferation, for treating any malignancy, and for inducing nerve, blood vessel or tissue regeneration in a particular tissue or organ.  
      A therapeutic delivery balloon is provided. In addition to the embodiments described above, one of skill in the art will realize that these examples are merely illustrative as numerous other embodiments may be implemented without departing from the spirit and scope of the present invention.