Methods and systems for toxin delivery to the nasal cavity

Abstract

Methods and systems for delivering toxin and toxin fragments to a patient's nasal cavity provide for both release of the toxin and delivery of energy which selectively porates target cells to enhance uptake of the toxin. The use of energy-mediated delivery is particularly advantageous with light chain fragment toxins which lack cell binding capacity.

What is claimed is: 
     
         1 . A system for treating a nasal condition in a patient, said system comprising:
 an apparatus insertable into a nasal cavity of the patient, the apparatus comprising an outer expandable member and an inner expandable member disposed within the outer expandable member and configured to expand within the nasal cavity, wherein expansion of the inner expandable member causes expansion of the outer expandable member such that the outer expandable member is placed in contact with a wall of the nasal cavity; and   a toxin either: (i) carried by the outer expandable member or (ii) disposed in a space between the outer and inner expandable members,   wherein the outer expandable member is configured to deliver the toxin to target cells in the wall of the nasal cavity.   
     
     
         2 . The system of  claim 1 , wherein the toxin comprises a light chain fragment of a neurotoxin substantially free of heavy chain fragments of the neurotoxin. 
     
     
         3 . The system of  claim 2 , wherein the neurotoxin consists of botulinum toxin. 
     
     
         4 . The system of  claim 3 , wherein the light chain fragment is derived from at least one of botulinum toxins A, B, C, D, E, F, and G. 
     
     
         5 . The system of  claim 1 , wherein the toxin comprises at least one of: a liquid, gel, foam, cream, lotion, or lyophilized compound. 
     
     
         6 . The system of  claim 1 , wherein the inner expandable member comprises a low volume configuration adapted to facilitate insertion into the nasal cavity and an expanded volume configuration adapted to place the outer expandable member in contact with the wall of the nasal cavity. 
     
     
         7 . The system of  claim 1 , wherein the expansion of the inner expandable member facilitates delivery of the toxin from the outer expandable member. 
     
     
         8 . The system of  claim 1 , further comprising an impermeable lining separating the inner expandable member and the outer expandable member and configured to prevent the toxin from entering the inner member. 
     
     
         9 . The system of  claim 1 , wherein the outer expandable member comprises an outer balloon and the toxin is delivered through one or more pores of the outer balloon. 
     
     
         10 . The system of  claim 9 , wherein the inner expandable member comprises an inner balloon. 
     
     
         11 . The system of  claim 10 , further comprising a fluid introduced into the inner balloon to expand the inner expandable member. 
     
     
         12 . The system of  claim 9 , wherein the inner expandable member comprises a wire, frame, or scaffold. 
     
     
         13 . The system of  claim 1 , wherein the outer expandable member comprises a sponge. 
     
     
         14 . The system of  claim 13 , wherein the inner expandable member comprises a spring element. 
     
     
         15 . The system of  claim 1 , wherein the outer expandable member comprises at least one of: a mesh pad, porous polymer, bioresorbable coating, or muco-adhesive surface. 
     
     
         16 . The system of  claim 1 , further comprising an energy applicator configured for applying energy to the target cells to enhance delivery of the toxin to the target cells. 
     
     
         17 . The system of  claim 16 , wherein the energy is applied to the target cells under conditions which cause poration of cell membranes of the target cells. 
     
     
         18 . The system of  claim 17 , wherein the energy applicator is adapted to apply energy comprising at least one of: electrical pulses, acoustic pulses, x-ray energy, or microwave energy. 
     
     
         19 . A method for treating a nasal condition in a patient, said method comprising:
 inserting an apparatus into a nasal cavity of the patient, wherein the apparatus comprises an inner and an outer expandable member;   expanding the inner expandable member thereby causing the outer expandable member to expand and contact a wall of the nasal cavity; and   delivering a toxin from the outer expandable member to target cells in the wall of the nasal cavity.   
     
     
         20 . The method of  claim 19 , wherein the toxin comprises a light chain fragment of a neurotoxin substantially free of heavy chain fragments of the neurotoxin. 
     
     
         21 . The method of  claim 20 , wherein the neurotoxin consists of botulinum toxin. 
     
     
         22 . The method of  claim 21 , wherein the light chain fragment is derived from at least one of botulinum toxins A, B, C, D, E, F, and G. 
     
     
         23 . The method of  claim 19 , wherein the inner expandable member is disposed within the outer expandable member. 
     
     
         24 . The method of  claim 23 , wherein the toxin is either: (i) carried by the outer expandable member or (ii) disposed in a space between the outer and inner expandable members. 
     
     
         25 . The method of  claim 19 , wherein the outer expandable member comprises an outer balloon and delivering the toxin comprises passing the toxin through one or more pores of the outer balloon. 
     
     
         26 . The method of  claim 25 , wherein the inner expandable member comprises an inner balloon. 
     
     
         27 . The method of  claim 26 , wherein expanding the inner expandable member comprises filling the inner balloon with a fluid. 
     
     
         28 . The method of  claim 19 , further comprising applying energy to the target cells to enhance delivery of the toxin to the target cells. 
     
     
         29 . The method of  claim 28 , wherein applying energy to the target cells comprises porating cell membranes of the target cells. 
     
     
         30 . The method of  claim 19 , wherein expanding the inner balloon substantially fills the nasal cavity, thereby inhibiting release of the toxin into portions of the nasal cavity other than the wall. 
     
     
         31 . The method of  claim 30 , wherein delivering the toxin comprises delivering a therapeutic dose to the wall of the nasal cavity while inhibiting release of the toxin into other portions of the nasal cavity.