Method and System for in Vivo Drug Delivery

• US 20080213355A1
• Filed: 07/11/2006
• Published: 09/04/2008
• Est. Priority Date: 07/22/2005
• Status: Abandoned Application

• Current Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Original Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Inventors: Bohmer, Marcel
• Application Number:
  US11/995,851
• Publication Number:
  US 20080213355A1
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00

Abstract

A system and method for polymeric drug delivery vehicles activated by ultrasound is disclosed herein. The system and method include polymeric particles, partially filled with a gas or a gas precursor, and partially filled with a liquid containing a drug. The drug is then released locally by application of ultrasound. Because the drug is dissolved, the delivery thereof is more efficient than for drugs incorporated with or in the polymeric shell of such particles.

Claims

1. An in vivo polymeric drug delivery system, the system comprising:

therapeutic drug dissolved in a solvent, the solvent not being removable by lyophilization;

one of a gas and a gas precursor combined with the therapeutic drug dissolved in the solvent; and

a polymer shell, wherein the drug is released from within the polymer shell by application of ultrasound to rupture the polymer shell.

2. The system of claim 1, wherein the polymer shell is partially filled with the therapeutic drug dissolved in the solvent and partially filled with one of the gas and the gas precursor.

3. The system of claim 1, wherein both the solvent and gas precursor are liquids and one of the two liquids is phase converted using ultrasound.

4. The system of claim 1, wherein an inside surface defining the polymer shell is hydrophobic.

5. The system of claim 4, wherein the polymer shell is a polymer with one of an alkyl and a fluorinated end group.

6. The system of claim 1, wherein an outside surface defining the polymer shell includes a targeting moiety.

7. The system of claim 1, wherein the solvent is at least one of a higher alkane and an oil.

8. The system of claim 1, wherein the polymer shell is a biodegradable polymer including one of a polylactide, polyglycolide, polycaprolactone, polycyanoacrylate and copolymer of one of the foregoing.

9. The system of claim 8, wherein the biodegradable polymer is pegylated to improve circulation in blood.

10. The system of claim 1, wherein the system is substantially monodisperse

11. The system of claim 1, wherein the polymer shell is formed using drop-by-drop emulsification including one of inkjet printing, cross-flow emulsification and micro-channel emulsification.

12. A method for in vivo polymeric drug delivery using ultrasound, the method comprising:

dissolving a therapeutic drug in a solvent, the solvent not being removed by lyophilization;

combining one of a gas and a gas precursor with the therapeutic drug dissolved in a solvent, the gas and the gas precursor being removable by lyophilization;

forming a polymer shell by emulsification and lyophilization of the mixture of the therapeutic drug dissolved in the solvent combined with one of the gas and the gas precursor; and

applying ultrasound to rupture the polymer shell and release the drug in vivo.

13. The method of claim 12, wherein the polymer shell is partially filled with the therapeutic drug dissolved in the solvent and partially filled with one of the gas and the gas precursor.

14. The method of claim 12, wherein both the solvent and gas precursor are liquids and one of the two liquids is phase converted using ultrasound.

15. The method of claim 12, wherein an inside surface defining the polymer shell is hydrophobic.

16. The method of claim 15, wherein the polymer shell is a polymer with one of an alkyl and a fluorinated end group.

17. The method of claim 12, wherein an outside surface defining the polymer shell includes a targeting moiety.

18. The method of claim 12, wherein the solvent is at least one of a higher alkane and an oil.

19. The method of claim 12, wherein the polymer shell is a biodegradable polymer including one of a polylactide, polyglycolide, polycaprolactone, polycyanoacrylate and copolymer of one of the foregoing.

20. The method of claim 19, wherein the biodegradable polymer is pegylated to improve circulation in blood.

21. The method of claim 12, further comprising

forming substantially monodisperse particles.

22. The method of claim 12, further comprising:

forming the polymer shell using drop-by-drop emulsification including one of inkjet printing, cross-flow emulsification and micro-channel emulsification.

23. A method for polymeric drug delivery activated by ultrasound, the method comprising:

preparing an emulsion of at least one polymer dissolved in a first solvent and a drug dissolved in a second solvent;

adding a non-solvent;

removing solvent from the emulsion by one of agitation and extraction leaving a liquid consisting of non-solvent for the polymer to be evaporated and solvent for the drug;

redispersing the capsules in a fluid medium;

injecting the fluid medium having the capsules in vivo; and

applying ultrasound to release the drug from the capsule.

24. The method of claim 23, further comprising:

freeze drying the capsules at a selected pressure not sufficient to remove the solvent in which the drug is dissolved.