Proteins represent a versatile biopolymer material for the preparation of nanoparticles due to their biocompatibility, biodegradability, and low immunogenicity. This study presents a protein-based nanoparticle system consisting of high surface PEGylated lysozyme polyethylene glycol-modified lysozyme (LYZmPEG). This protein modification leads to a solubility switch, which allows a nanoparticle preparation using a mild double emulsion method without the need of surfactants. The method allows the encapsulation of large hydrophilic payloads inside of the protein-based nanoparticle system. Native lysozyme (LYZ) was chosen as payload because of its innate activity as natural antibiotic. The mild particle preparation procedure retains the structure and activity of the enzyme which was successfully tested against the gram-positive bacteria strain M. Luteus. In comparison, the particle system shows no toxicity to human cells. This first report of a full protein-based particle material for the transport of large hydrophilic payloads opens up new therapeutic applications for biopolymer-based delivery systems.