The Effect of Elasticity of Gelatin Nanoparticles on the Interaction with Macrophages

Gelatin is a biocompatible, biodegradable, cheap, and nontoxic material, which is already used for pharmaceutical applications. Nanoparticles from gelatin (GNPs) are considered a promising delivery system for hydrophilic and macromolecular drugs. Mechanical properties of particles are recognized as an important parameter affecting drug carrier interaction with biological systems. GNPs offer the preparation of particles with different stiffness. GNPs were loaded with Fluorescein isothiocyanate-labeled 150 kDa dextran (FITC-dextran) yielding also different elastic properties. GNPs were visualized using atomic force microscopy (AFM), and force-distance curves from the center of the particles were evaluated for Young's modulus calculation. The prepared GNPs have Young's moduli from 4.12 MPa for soft to 9.8 MPa for stiff particles. Furthermore, cytokine release (IL-6 and TNF-alpha), cell viability, and cell uptake were determined on macrophage cell lines from mouse (RAW 264.7) and human (dTHP-1 cells, differentiated human monocytic THP-1 cells) origin for soft and stiff GNPs. Both particle types showed good cell compatibility and did not induce IL-6 and TNF-alpha release from RAW 264.7 and dTHP-1 cells. Stiffer GNPs were internalized into cells faster and to a larger extent.

Automated summary

Gelatin is a versatile material with biocompatibility, biodegradability, and low toxicity, making it suitable for pharmaceutical applications. Gelatin nanoparticles (GNPs) have great potential for delivering hydrophilic and macromolecular drugs. The mechanical properties of GNPs, particularly their stiffness, play a significant role in their interaction with biological systems. By loading GNPs with FITC-dextran and using atomic force microscopy (AFM), the Young's modulus of the GNPs was determined. The results showed that the prepared GNPs had different stiffness, ranging from 4.12 MPa to 9.8 MPa. In addition, the compatibility of the GNPs with macrophage cell lines from mouse and human origin was evaluated, demonstrating good cell compatibility and efficient cell uptake, especially for the stiffer GNPs.