De novo Drug Delivery Modalities for Treating Damaged Hearts: Current Challenges and Emerging Solutions

Figures

• 

  Figure 1. Schematic representing the intramyocardial delivery of growth factor-loaded formulations (nanoparticles, microspheres, and hydrogels) for localized and sustained delivery for repairing the damaged cardiac tissue.

• 

  Figure 2. Schematics representing the fabrication of mitochondria mimicking smart polyelectrolyte nanoparticle and their mechanism of action. (A) Structural mimic of organelle-like nanoparticle, (B) Functional similarity of the mitochondrion and organelle-like nanoparticle. (C) Fabrication of organelle-like nanoparticles by layer-by-layer approach. (D) Ischemia responsive activation of VEGF expression facilitated organelle-like nanoparticle and their antioxidant potential (70).

• 

  Figure 3. (A) Schematic representing cardiac stem cell (CSC) mimicking microspheres fabricated by coassembly of CSC-derived membranes on polymeric microspheres. (B,C) Fluorescence imaging of CSC (green) and microsphere (red) tagged with fluorescent dyes (D,E) SEM of blank microsphere and CSC coated microsphere. (F,G) Evaluation of CSC markers on fabricated hybrid microspheres. (H) Size analysis of hybrid microspheres and respective controls. (I) CSC antigen analysis of hybrid microspheres. (J–L) VEGF, IGF-1, and HGF growth factors release profiles from the hybrid microspheres, respectively (81).

• 

  Figure 4. (A) Schematics representing the protocol for large animal studies for smart hydrogel. (B) Photograph showing the position of the camera and an injection port. (C) Sequential representative images are displaying the administration of smart hydrogel. (D) Schematic representing the sectioning of the isolated heart. (E) Ex vivo NIR imaging of cardiac slices demonstrating the accumulation of injected smart hydrogel. (F) Fluorescence imaging of bFGF. (G,H) Quantitative and qualitative analysis of cytokines before and after administration of smart hydrogel. (I,J) The feasibility of minimally invasive catheter-based administration into the pericardial cavity in a human subject (103).