Mechano-sensitive microcapsules for drug delivery
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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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