Method for delivering bioactive agents into and through the mucosally-associated lymphoid tissues and controlling their release

• US 5,942,252 A
• Filed: 06/06/1995
• Issued: 08/24/1999
• Est. Priority Date: 10/24/1986
• Status: Expired due to Fees

• Current Assignee: Southwest Research Institute, UAB Research Foundation (University of Alabama System)
• Original Assignee: Southwest Research Institute, UAB Research Foundation (University of Alabama System)
• Inventors: Tice, Thomas R., Eldridge, John H., Staas, Jay K., Gilley, Richard M.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US08/469,463
• Time in Patent Office: 1,540 Days
• Field of Search: 424/489, 424/451, 424/464, 424/490, 424/426, 424/430, 424/434, 424/435, 424/436, 424/501, 514/772.3, 514/912
• US Class Current: 424/501
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 424/81 involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, immunotolerance, or anergy
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

A method, and compositions for use therein capable, of delivering a bioactive agent to an animal entailing the steps of encapsulating effective amounts of the agent in a biocompatible excipient to form microcapsules having a size less than approximately ten micrometers and administering effective amounts of the microcapsules to the animal. A pulsatile response is obtained, as well as mucosal and systemic immunity.

Claims

1. A method of increasing the bioavailability of a bioactive agent which is taken up by the mucosally-associated lymphoid tissues of an animal comprising orally, nasally, rectally, vaginally, ophthalmically, or oral inhalationally administering an effective amount of microcapsules to said animal, wherein said microcapsules comprise said bioactive agent encapsulated in a biocompatible excipient and wherein said microcapsules are of a size of between approximately 1 micrometer and approximately 10 micrometers.

2. The method of claim 1, wherein said microcapsules are between approximately 1 micrometer and approximately 5 micrometers.

3. The method of claim 1, wherein said bioactive agent is a drug, nutrient, immunomodulator, lymphokine, monokine, cytokine, or antigen.

4. The method of claim 1, wherein said bioactive agent is a drug.

5. The method of claim 1, wherein said bioactive agent is an antigen.

6. The method of claim 1, wherein said bioactive agent further includes a cytokine.

7. The method of claim 6, wherein said microcapsules further include an adjuvant.

8. The method of claim 1, wherein said bioactive agent is a cytokine and said microcapsules further include an adjuvant.

9. The method of claim 1, wherein said bioactive agent comprises a peptide, protein, or a nucleic acid.

10. The method of claim 1, wherein the administering is orally.

11. The method of claim 1, wherein said biocompatible excipient is a poly(lactide-co-glycolide), poly(lactide), poly(glycolide), copolyoxalate, polycaprolactone, poly(lactide-co-caprolactone), poly(esteraminde), polyorthoester, poly(p-hydroxybutyric acid), polyanhydride, or a mixture thereof.

13. The method of claim 4, wherein the administering is orally.

12. A method of increasing the bioavailability of a bioactive agent to an animal comprising orally, nasally, rectally, vaginally, ophthalmically, or oral inhalationally administering an effective amount of microcapsules to said animal, wherein said microcapsules comprise said bioactive agent encapsulated in a biocompatible excipient and wherein said microcapsules are of a size of less than approximately 10 micrometers.

14. The method of claim 12, wherein the administering is orally.

15. The method of claim 12, wherein the bioactive agent is a drug.

16. The method of claim 15, wherein the administering is orally.

17. The method of claim 12, wherein the microcapsules are of a size of less than about 5 μ

m.

18. The method of claim 17, wherein the administering is orally.

19. The method of claim 17, wherein the bioactive agent is a drug.

20. The method of claim 19, wherein the administering is orally.

21. The method of claim 18, wherein said microcapsules are between approximately 1 micrometer and approximately 5 micrometers.

22. The method of claim 19, wherein said microcapsules are between approximately 1 micrometer and approximately 5 micrometers.

23. The method of claim 20, wherein said microcapsules are between approximately 1 micrometer and approximatelv 5 micrometers.