Ultrasound-Triggerable Agents for Tissue Engineering

Patent metadata

Field	Value
Publication number	US-2016279059-A1
Application number	US-201615055263-A
Country	US
Kind code	A1
Filing date	Feb 26, 2016
Priority date	Jun 8, 2012
Publication date	Sep 29, 2016
Grant date	—

Abstract

The present invention is directed to compositions and methods for delivering a tissue scaffold comprising ultrasound-triggerable agents to an individual.

First claim

1 . A method of delivering an effective amount of a therapeutic agent to an individual in need thereof comprising administering to the individual a device comprising:
(a) a tissue scaffold; (b) an emulsion that comprises a perfluorocarbon (PFC) droplet comprising the therapeutic agent in the interior thereof, the PFC having a mean droplet diameter that is at least about 20 micrometers (μm), and the emulsion having a volume fraction in the tissue scaffold of at least about 1% volume: volume.

2 . A method of delivering an effective amount of a therapeutic agent to an individual in need thereof comprising administering to the individual a device comprising:
(a) a tissue scaffold; and (b) an emulsion comprising a first population of perfluorocarbon (PFC) droplets comprising a therapeutic agent in the interior thereof, said first population of PFC droplets having the property of vaporizing at a first ultrasound frequency and/or acoustic pressure threshold.

3 . The method of claim 2 , further comprising a second population of PFC droplets, said second population of PFC droplets having the property of vaporizing at a second ultrasound frequency and/or acoustic pressure threshold that is different than the first ultrasound frequency and/or acoustic pressure threshold.

4 . The method of claim 2 , further comprising a progenitor cell.

5 . The method of claim 4 wherein the progenitor cell is a fibroblast, a chondrocyte, an osteoblast, a skeletal myocyte, a cardiac myocyte, a mesenchymal progenitor cell, a hematopoietic progenitor cell, a satellite cell, a neural progenitor cell, a pancreatic progenitor cell, a blast cell or a combination thereof.

6 . The method of claim 2 wherein the emulsion is a double emulsion comprising a primary emulsion and a secondary emulsion.

7 . The method of claim 6 wherein the primary emulsion comprises water-in-PFC, and the secondary emulsion comprises water-in-PFC-in-water.

8 . The method of claim 2 , further comprising a surfactant.

9 . The method of claim 8 , wherein a first surfactant stabilizing the primary emulsion is a triblock copolymer, and a second surfactant stabilizing the secondary emulsion is an aqueous soluble surfactant.

10 . The method of claim 9 wherein the triblock copolymer comprises a perfluoroether and polyethylene glycol.

11 . The method of claim 9 wherein the aqueous soluble surfactant is selected from the group consisting of a protein, a lipid, an ionic copolymer and a non-ionic copolymer.

12 . The method of claim 2 wherein initial pore size of the tissue scaffold is at least about 100 nanometers (nm).

13 . The method of claim 2 wherein vaporization of the PFC droplet results in a final pore size of the tissue scaffold of at least about 40 tm and up to about 5 millimeters (mm).

14 . The method of claim 2 , wherein the density of the tissue scaffold is between about 100 μg/mL to about 100 mg/mL fibrinogen.

15 . The method of claim 2 wherein the device is implantable.

16 . The method of claim 2 wherein the device is topical.

17 . The method of claim 2 wherein the therapeutic agent is selected from the group consisting of a polypeptide, a peptide, a polynucleotide, a viral particle, a gas, a contrast agent and a small molecule.

18 . The method of claim 2 wherein release of the therapeutic agent is controlled spatially.

19 . The method of claim 2 wherein release of the therapeutic agent is controlled temporally.

Assignees

• Univ Michigan Regents

Inventors

• Fabiilli Mario L
• Wilson Christopher
• Padilla Frederic
• Martin-Saavedra Francisco

Classifications

• A61K35/00

  Medicinal preparations containing materials or reaction products thereof with undetermined constitution · CPC title

• A61L2300/62

  Encapsulated active agents, e.g. emulsified droplets · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61K38/1825

  Fibroblast growth factor [FGF] · CPC title

• A61K9/0014

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title