USRE37053EExpiredUtility

Particles incorporating surfactants for pulmonary drug delivery

95
Assignee: MASSACHUSETTS INST TECHNOLOGYPriority: May 24, 1996Filed: Jul 12, 1999Granted: Feb 13, 2001
Est. expiryMay 24, 2016(expired)· nominal 20-yr term from priority
Inventors:Justin HanesDavid A. EdwardsCarmen EvoraRobert S. Langer
A61K 31/135A61K 38/38A61K 38/28A61K 9/1617A61K 9/1623A61K 9/1641A61K 31/137A61K 9/1647A61K 9/1658A61K 9/0073
95
PatentIndex Score
219
Cited by
123
References
33
Claims

Abstract

Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm 3 and a mass mean diameter between 5 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear α-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 μm, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
       1. A particulate composition for drug delivery to the pulmonary system comprising: 
       biodegradable particles incorporating a therapeutic, prophylactic or diagnostic agent and a surfactant, wherein the particles have a tap density less than 0.4 g/cm 3  and a mean diameter between 5 μm and 30 μm effective to yield an aerodynamic diameter of the particles of between approximately one and three microns.  
     
     
       2. The system of claim  1  wherein at least 50% of the particles have a mass mean diameter between 5 μm and 30 μm. 
     
     
       3. The composition of claim  1  wherein at least 50% of the particles have a mean diameter between 5 μm and 15 μm and a tap density less than 0.1 g/cm 3 . 
     
     
       4. The composition of claim  1  further comprising a pharmaceutically acceptable carrier for administration to the lungs. 
     
     
       5. The composition of claim  1  wherein the particles comprise a biodegradable polymer. 
     
     
       6. The composition of claim  1  wherein the particles comprise a polyester. 
     
     
       7. The composition of claim  1  wherein the particles comprise an excipient or a fatty acid. 
     
     
       8. The composition of claim  1  wherein the particles have an irregular surface structure. 
     
     
       9. The composition of claim  1  wherein the surfactant is coated on the surface of the particle. 
     
     
       10. The composition of claim  1  wherein the surfactant is incorporated within and on the surface of the particle. 
     
     
       11. The composition of claim  1  wherein the therapeutic agent is selected from the group consisting of proteins, polysaccharides, lipids, nucleic acids and combinations thereof. 
     
     
       12. The composition of claim  1  wherein the therapeutic agent is selected from the group consisting of a ribonucleic acid and a deoxyribonucleic acid. 
     
     
       13. The composition of claim  1  wherein the therapeutic agent is selected from the group consisting of insulin, calcitonin, leuprolide and albuterol. 
     
     
       14. The composition of claim  1  wherein the surfactant is selected from the group consisting of a fatty acid, a phospholipid, and a poloxamer. 
     
     
       15. The composition of claim  1  wherein the surfactant is a phosphoglyceride. 
     
     
       16. The composition of claim  1  wherein the surfactant is dipalmitoyl L-α-phosphatidylcholine. 
     
     
       17. A method for drug delivery to the pulmonary system comprising: 
       administering to the respiratory tract of patient in need of treatment an effective amount of biodegradable particles incorporating a therapeutic, prophylactic or diagnostic agent and a surfactant,  
       wherein the particles have a tap density less than about 0.4 g/cm 3  and a mean diameter of between 5 μm and 30 μm effective to yield an aerodynamic diameter of the particles of between approximately one and three microns.  
     
     
       18. The method of claim  17  wherein at least 50% of the administered particles have a mean diameter between 5 μm and 15 μm. 
     
     
       19. The method of claim  18  wherein at least 50% of the administered particles have a mean diameter between 5 μm and 15 μm and a tap density of less than about 0.1 g/cm 3 . 
     
     
       20. The method of claim  17  wherein the particles comprise a biodegradable polymer. 
     
     
       21. The method of claim  17  wherein the particles comprise a polyester. 
     
     
       22. The method of claim  17  wherein the particles comprise an excipient. 
     
     
       23. The method of claim  21  wherein the particles have an irregular surface structure. 
     
     
       24. The method of claim  17  for delivery to the alveolar zone of the lung wherein at least 90% of the particles have a mean diameter between about 9 μm and 11 μm and a tap density less than 0.1 g/cm 3 . 
     
     
       25. The method of claim  17  wherein the therapeutic agent is selected from the group consisting of proteins, polysaccharides, lipids, nucleic acids and combinations thereof. 
     
     
       26. The method of claim  17  wherein the therapeutic agent selected from the group consisting of a ribonucleic acid and a deoxyribonucleic acid. 
     
     
       27. The method of claim  17  wherein the therapeutic agent is selected from the group consisting of insulin, calcitonin, leuprolide and albuterol. 
     
     
       28. The method of claim  17  wherein the particles are administered in combination with a pharmaceutically acceptable carrier for administration to the respiratory tract. 
     
     
       29. The method of claim  17  wherein the surfactant is selected from the group consisting of a fatty acid, a phospholipid, and a poloxamer. 
     
     
       30. The method of claim  17  wherein the surfactant is a phosphoglyceride. 
     
     
       31. The method of claim  17  wherein the surfactant is dipalmitoyl L-α-phosphatidylcholine. 
     
     
       32. The method of claim  17  wherein the surfactant is coated on the surface of the particle. 
     
     
       33. The method of claim  17  wherein the surfactant is incorporated within and on the surface of the particle.

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