Microparticle compositions for controlled delivery of telmisartan and actinomycin D

Patent metadata

Field	Value
Publication number	US-11951152-B1
Application number	US-202017025277-A
Country	US
Kind code	B1
Filing date	Sep 18, 2020
Priority date	Sep 18, 2019
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

Abstract

This disclosure is directed to therapeutic compositions, and more particularly to microparticle compositions for the controlled delivery of telmisartan and actinomycin D.

First claim

What is claimed is:

1. A therapeutic composition comprising:
a plurality of liposomal microparticles;
a plurality of terephthalaldehyde (TPA)-crosslinked chitosan nanoparticles encapsulated within the liposomal microparticles, wherein the TPA-crosslinked chitosan nanoparticles are loaded with actinomycin D; and
a plurality of tripolyphosphate (TPP)-crosslinked chitosan nanoparticles encapsulated within the liposomal microparticles, wherein the TPP-crosslinked chitosan nanoparticles are loaded with telmisartan.

2. The therapeutic composition of claim 1 , wherein the liposomal microparticles have an average particle diameter ranging from about 25 to about 55 microns.

3. The therapeutic composition of claim 1 , wherein the liposomal microparticles comprise dipalmitoylphosphatidylcholine (DPPC).

4. The therapeutic composition of claim 1 , wherein the TPA-crosslinked chitosan nanoparticles have an average particle diameter ranging from about 300 nm to about 700 nm at a pH of greater than about 7.

5. The therapeutic composition of claim 1 , wherein the TPA-crosslinked chitosan nanoparticles have a zeta potential ranging from about 2 mV to about 5 mV at a pH of greater than about 7.

6. The therapeutic composition of claim 1 , wherein the TPA-crosslinked chitosan nanoparticles release actinomycin D at a pH of less than about 7.

7. The therapeutic composition of claim 6 , wherein the average particle diameter of the TPA-crosslinked chitosan nanoparticles increases by an amount ranging from about 100 nm to about 300 nm at a pH of less than about 7.

8. The therapeutic composition of claim 6 , wherein the zeta potential of the TPA-crosslinked chitosan nanoparticles increases by an amount ranging from about 5 mV to about 15 mV at a pH of less than about 7.

9. The therapeutic composition of claim 6 , wherein the TPA-crosslinked chitosan nanoparticles release at least 25% of the loaded actinomycin D within 30 minutes at a pH of less than about 7.

10. The therapeutic composition of claim 1 , wherein the therapeutic composition further comprises acetazolamide, wherein acetazolamide is conjugated to a surface of the TPA-crosslinked chitosan nanoparticles.

11. The therapeutic composition of claim 1 , wherein the TPP-crosslinked chitosan nanoparticles have an average particle diameter from about 50 nm to about 500 nm.

12. The therapeutic composition of claim 1 , wherein the TPP-crosslinked chitosan nanoparticles have a zeta potential ranging from about 5 mV to about 50 mV.

13. The therapeutic composition of claim 1 , wherein the TPP-crosslinked chitosan nanoparticles provide sustained release of telmisartan.

14. The therapeutic composition of claim 1 , wherein the therapeutic composition further comprises acetazolamide, wherein acetazolamide is conjugated to a surface of the TPP-crosslinked chitosan nanoparticles.

15. The therapeutic composition of claim 1 , further comprising one or more additional therapeutic agents.

16. The therapeutic composition of claim 1 formulated for delivery to the lung.

17. A method of treating lung cancer in a subject comprising administering a therapeutically effective amount of the composition of claim 1 to the subject.

18. The method of claim 17 , wherein the composition is administered to the lung.

Assignees

• Univ South Florida
• The Us Gov As Represented By The Department Of Veteran Affairs

Inventors

• Mohapatra Subhra
• Mohapatra Shyam S
• Markoutsa Eleni
• Gonzalez Alejandro J
• Jadhav Heta N

Classifications

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/5161

  Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin · CPC title

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K9/1652

  Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623) · CPC title