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 method for delivering toxins to target cells in a nasal membrane of a patient, said method comprising:
introducing a toxin to a region proximate the target cells, said toxin comprising a light chain fragment of a neurotoxin and being substantially free of heavy chain fragments of the neurotoxin; and
applying energy to the target cells to enhance delivery of the toxin to the cells.
2. A method as in claim 1 , wherein the region comprises at least one paranasal sinus, a main nasal passage or a nasal turbinate.
3. A method as in claim 1 , wherein the region comprises substantially the entire nasal cavity.
4. A method as in claim 1 , wherein the region comprises the nasopharynx.
5. A method as in claim 1 , wherein the target cells comprise epithelial or goblet cells.
6. A method as in claim 1 , wherein the energy is selectively applied to target cells within the region where the toxin has been introduced.
7. A method as in claim 1 , wherein the energy is applied non-selectively within the region where the toxin has been introduced.
8. A method as in claim 1 , wherein the patient suffers from or is at risk of suffering from rhinorreah.
9. A method as in claim 1 , wherein the patient suffers from or is at risk of suffering from sinus headaches.
10. A method as in claim 1 , wherein the patient suffers from or is at risk of suffering from migraine headaches.
11. A method as in claim 1 , wherein the neurotoxin consists of botulinum toxin.
12. A method as in claim 11 , wherein the light chain fragment is derived from at least one of botulinum toxins A, B, C, D, E, F, and G.
13. A method as in claim 1 , wherein the energy applied to the targeted region is an electric pulse.
14. A method as in claim 13 , wherein the electric pulse is applied from between 1V to 500V.
15. A method as in claim 13 , wherein the electric pulse is an RF signal.
16. A method of claim 13 , wherein the electric pulse is pulsed for durations between 5 microseconds to 100 milliseconds.
17. A method as in claim 13 , wherein the electric pulse is produced by a DC power source.
18. A method as in claim 13 , wherein the electric pulse is produced by an AC power source.
19. A method as in claim 1 , wherein the energy applied to the target region is ultrasonic.
20. A method as in claim 1 , wherein the energy applied to the targeted region is an x-ray beam.
21. A method as in claim 1 , wherein the energy applied to the targeted region is focused ultrasound.
22. A method as in claim 1 , wherein the energy applied to the targeted region is microwave.
23. A method as in claim 1 , wherein the toxin is introduced to the target region through a catheter.
24. A method as in claim 23 , wherein the toxin is introduced through a balloon on the catheter.
25. A method as in claim 24 , wherein the balloon is porous and the toxin is introduced through the balloon.
26. A method as in claim 23 , wherein the toxin is introduced through a needle on the catheter.
27. A method as in claim 23 , wherein the toxin is aerosolized from the catheter.
28. A method as in claim 23 , wherein energy is applied from a source on the catheter.
29. A method as in claim 28 , wherein acoustic energy is applied from a transducer on the catheter.
30. A method as in claim 28 , wherein electrical energy is applied from an electrode on the catheter.
31. A method as in claim 1 , wherein the energy is delivered from a source external to the patient.
32. A method as in claim 31 , wherein the source is an acoustic energy transducer.
33. A method as in claim 32 , wherein the acoustic energy transducer is a focused ultrasound transducer.
34. A method as in claim 1 , wherein applying energy to the target cells further comprises applying energy to the target cells under conditions which cause poration of the cell membranes.
35. A method as in claim 28 , wherein microwave energy is applied from an antenna on the catheter.