Protein-loaded comb-shape copolymer-based pH-responsive nanoparticles to improve the stability of proteins

Extensive studies have shown that poly(lactide-co-glycolide) (PLGA) and its derivatives are excellent biomaterials for drug delivery systems. However, their use in protein delivery is limited due to their harsh internal pH environment. In this study, we designed an amphiphilic comb-shaped copolymer, lactobionic acid-poly(ethylene oxide)-epsilon-polylysine-g-PLGA (LPEP), for protein delivery. Depending on the ratio of PLGA contents, the internal pH of LPEP nanoparticles (NPs) was adjustable, which was verified by a quantitative ratiometric method. The protein delivery system was able to meet the needs of the appropriate pH microclimate for the integrity of proteins. Circular dichroism spectroscopy revealed that the protein released from LPEP NPs was more stable than that released from PLGA NPs. In addition, cytotoxicity studies involving HL-7702 cells and acute toxicity experiments in Kunming mice showed that the NPs had good biocompatibility. In vivo experiments showed the circulation time and tissue distribution of LPEP NPs. Taken together, our results suggest that the LPEP NP system is a promising candidate for protein delivery.