Comparative Analysis of Two Elastic Types of Surface‐Crosslinked Gelatin Nanoparticles as Suitable Systems for Macromolecular Drug Delivery

Abstract With a steadily rising number of novel biopharmaceuticals in development, the demand for applicable delivery systems for macromolecular drugs persists. Polymeric nanoparticles, consisting of the natural product gelatin, present beneficial attributes for this application. To stabilize those nanoparticles without interfering with encapsulated macromolecules, surface‐crosslinked gelatin particles are developed and thoroughly characterized for their physicochemical and mechanical properties. With only limited data available for the latter, investigating the elastic properties can offer a more comprehensive understanding of the crosslinking processes involved and of the gelatin particles’ potential applications. In this study, protocols for surface‐crosslinked gelatin particles type A (GNP‐A) and B (GNP‐B) are described. Significant differences between the two types of gelatin are reported regarding their physicochemical and mechanical properties. GNP‐A consists of a lower crosslinking degree, leading to pronounced swelling in aqueous environments and softer nanoparticles. They possess contrary properties compared to the more extensively crosslinked and stiffer GNP‐B. However, this doesn't affect encapsulation efficiency, allowing to develop nanoparticulate systems suitable for various applications by adjusting the particle properties while maintaining the same drug load. These findings provide a deeper understanding of polymeric gelatin particles and reveal the importance of investigating the mechanical properties of drug delivery systems during pharmaceutical development.