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Mechano-sensitive microcapsules for drug delivery

Inactive Publication Date: 2018-06-21
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a method for delivering therapy to a subject using mechanically-activated microcapsules. These microcapsules have a rupture profile that allows them to release their active ingredients when they are subjected to mechanical loads. The method includes identifying the rupture profile based on the expected mechanical loads and creating mechanically-activated microcapsules with that rupture profile. The microcapsules can be delivered to a specific region of the body and will rupture in response to the mechanical loads in that region. The invention also includes the use of mechanically-activated microcapsules with multiple rupture profiles for delivering multiple agents with different functions and timelines of release.

Problems solved by technology

However, there are no controlled delivery vehicles that have been tuned for triggered release in response to mechanical loading, deformation, or stress.

Method used

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  • Mechano-sensitive microcapsules for drug delivery
  • Mechano-sensitive microcapsules for drug delivery
  • Mechano-sensitive microcapsules for drug delivery

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0058]Fabrication of mechanically-activated microcapsules (MAMCs) and determination of how variations in fabrication parameters influence the structure-release properties of individual MAMCs.

[0059]In this first formulation, microcapsules were 100 μm in diameter with a shell thickness of 1 μm, and the shell was doped with a fluorescent dye (Nile Red) to enable visualization (FIG. 2a). To demonstrate mechano-activation, a single layer of MAMCs was subjected to increasing levels of load using a mechanical testing device (FIG. 2a). Results showed graded microcapsule rupture and release of FITC-dextran with increasing load (FIG. 2b). Intact microcapsules served as negative controls and sheared microcapsules (completely devoid of FITC-dextran due to complete rupture) served as positive controls. Fluorescent intensity of the buffer solution (indicating FITC-dextran release) correlated with load. Similar activity assays can be used to directly measure cumulative drug release for a given app...

example 2

[0070]In this example, the effects of polymer degradation of MAMC shells at physiologic temperature (37° C.) on mechano-activation were explored. Using the same parallel plate technique as described above in Example 1, MAMCs were tracked over a period of 14 days at different loads between 0 and 1 Newton, with 5 Newtons as a completely ruptured control. See FIGS. 4a and 4b. The group of MAMCs demonstrating the highest resistance to load from Example 1 (t / D of 0.009 and outer diameter of 105 μm) was used. Within the first three days of incubation at 37° C., the mechano-sensitivity of the MAMCs was unaffected. However, by day 7, the microcapsule mechanical release profile is significantly affected by application of load. See FIGS. 4b and 4c. This demonstrates that degradation of the polymer shell has a marked effect on mechanically controlled rupture and release of the MAMCs.

[0071]A similar methodology was carried out over 14 days using three different classes of MAMCs. See FIGS. 5a an...

example 3

Microcapsule Mechano-Activation in 3D Hydrogels.

[0073]In this example, the deformation of MAMCs embedded in 3D matrices (analogous to engineered constructs mimicking cartilage) was explored. To validate mechano-activation in a three-dimensional (3D) construct, microcapsules were embedded in 30% photo-crosslinked poly(ethylene glycol) diacrylate (PEGDA). See FIG. 9c. This hydrogel was chosen because its stiffness is comparable to native cartilage and matured engineered cartilage. Using a custom micromechanical compression device mounted on a confocal microscope (FIG. 7a), MAMC-laden hydrogels were compressed in unconfined compression (0-20% strain, steps of 4%, followed by compression until hydrogel failure). MAMCs deformed with increasing hydrogel compression, becoming ellipsoid at 20% strain and visibly rupturing at 60% strain (FIGS. 7b and 7d). FIG. 7b depicts the performance of MAMCs embedded in 3D gel matrix, as a function of applied strain; FIG. 7b further demonstrates how the ...

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Abstract

Embodiments of the present invention relate to mechanically-activated microcapsules (MAMCs) for controlled drug-delivery, wherein the MAMCs release one or more active ingredients in response to mechanical stimuli in a subject's body. The MAMCs provide a platform for stimulating biological regeneration, biological repair, modifying disease, and / or controlling disease in mechanically-loaded musculoskeletal tissues.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 62 / 169286, entitled MECHANO-SENSITIVE MICROCAPSULES FOR DRUG DELIVERY, filed Jun. 1, 2015, the contents of which are incorporated by reference herein in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to mechano-sensitive microcapsules for drug delivery, and methods of using the same.BACKGROUND OF THE INVENTION[0003]In comparison to conventional systemic delivery of therapeutics, controlled drug delivery has several advantages, including localized delivery to specific locations, maintenance of drug concentrations within a desired therapeutic range, and preservation of therapeutic activity for long-term administration. One particularly desirable feature of these systems is self-regulation, wherein physiological feedback actively controls release kinetics. Self-regulating delivery systems often rely on internal triggers for release, such as tempera...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K38/18A61P19/04
CPCA61K9/5031A61K9/5089A61K38/1841A61P19/04B01J13/02A61K9/0024A61K9/1075
Inventor LEE, DAEYEONMAUCK, ROBERT L.DODGE, GEORGE R.TU, FUQUANMOHANRAJ, BHAVANA
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA