A Freezing and Thawing Method for Fabrication of Small Gelatin Nanoparticles with Stable Size Distributions for Biomedical Applications

Background:: Gelatin, a natural polymer, has a number of advantages as a material for fabricating nanoparticles, such as its hydrophilicity, biodegradability, nontoxicity, and biocompatibility, as well as low cost. Despite these various advantages, gelatin-based nanoparticles still have critical limitation for biomedical applications due to their relatively larger size than those of other materials. Methods:: In this study, a new strategy to design and fabricate small gelatin nanoparticles (GNPs) was proposed. The technique was based on the natural phenomenon where with decreasing temperature, the compression between the molecules of substances increases and the volume shrinks. Results:: The average size of the fabricated small GNPs was less than 100 nm and their gelatin properties (including non-cytotoxicity) were well maintained. The drug release profiles of the GNPs were confirmed, for which a simple mathematical model based on the conventional diffusion equation was proposed. There was a burst of drug release in the first 3 days, with different release profiles according to the concentration of model drugs loaded onto the GNPs. It was also demonstrated that the drug release profiles of the proposed mathematical model were consistent with the experimental results. Conclusion:: Our work proposes that these small GNPs could be used as efficient drug and gene delivery and tissue engineering platforms for various biomedical applications.