Methods and systems for toxin delivery to the nasal cavity
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.
1. A system for delivering toxins to target cells in a nasal membrane, said system comprising:
a catheter adapted to introduce a toxin to a region proximate the target cells;
an energy applicator configured for applying energy to the target cells under conditions which cause poration of the cell membranes to enhance delivery of the toxin; and
a source of toxin suitable for introduction from the catheter, wherein the toxin comprises a light chain fragment of a neurotoxin and being substantially free of heavy chain fragments of the neurotoxin.
2. A system as in claim 1 , wherein the energy applicator is adapted to selectively apply energy to target cells within the region where toxin has been introduced.
3. A system as in claim 1 , wherein the energy applicator is adapted to apply energy non-selectively within the region where toxin has been introduced.
4. A system as in claim 1 , wherein the neurotoxin consists of botulinum toxin.
5. A system as in claim 1 , wherein the light chain fragment is derived from at least one of botulinum toxins A, B, C, D, E, F, and G.
6. A system as in claim 1 , wherein the energy applicator is adapted to apply an electric pulse of between 1 v and 500V to the targeted region.
7. A system as in claim 6 , wherein the electric pulse is an RF signal.
8. A system as in claim 6 , wherein the electric pulse is pulsed for durations between 5 microseconds to 100 milliseconds.
9. A system as in claim 6 , wherein the electric pulse is produced by a DC power source.
10. A system as in claim 6 , wherein the electric pulse is produced by an AC power source.
11. A system as in claim 1 , wherein the energy applicator is adapted to apply ultrasonic energy to the targeted region.
12. A system as in claim 1 , wherein the energy applicator is adapted to apply an x-ray beam to the targeted region.
13. A system as in claim 1 , wherein the energy applicator is adapted to apply focused ultrasound to the targeted region.
14. A system as in claim 1 , wherein the energy applicator is adapted to apply microwave to the targeted region.
15. A system as in claim 1 , wherein the toxin is introduced by a balloon on the catheter.
16. A system as in claim 15 , wherein the balloon comprises one or more pores and the toxin is introduced through the pores of the balloon.
17. A system as in claim 15 , wherein the toxin is introduced through a needle on the catheter.
18. A system as in claim 15 , wherein the toxin is aerosolized from the catheter.
19. A system as in claim 1 , wherein energy applicator is on the catheter.
20. A system as in claim 19 , wherein energy applicator applies acoustic energy from a transducer on the catheter.
21. A system as in claim 19 , wherein energy applicator applies electrical energy from an electrode on the catheter.
22. A system as in claim 1 , wherein the applicator applies energy from a source external to the patient.
23. A system as in claim 22 , wherein the source further comprises an acoustic energy transducer.
24. A system as in claim 23 , wherein the acoustic energy transducer further comprises a focused ultrasound transducer.
25. A system as in claim 1 , wherein the toxin is introduced through a membrane supported on a scaffold on the catheter.
26. A system as in claim 1 , wherein the toxin is introduced by a needless injector.
27. A system as in claim 1 , wherein the energy applicator comprises a wave guide configured to be positioned within a nasal passageway.
28. A system as in claim 15 , wherein the balloon is configured to be positioned within a nasal passageway.
29. A system as in claim 15 , wherein the balloon is configured to be positioned outside of a sinus cavity.
30. A system as in claim 22 , wherein the source further comprises a microwave antenna.