A novel rosiglitazone-phosphatidylserine composite nanoparticle mediated targeted drug delivery to macrophages for treatment of ulcerative colitis.

AIMS: The treatment of ulcerative colitis(UC) remains a significant challenge contributing to the growing global healthcare burden. Efficient clearance of apoptotic cells is a crucial mechanism for tissue repair and maintenance of homeostasis following inflammatory damage. Macrophages critically govern the balance between inflammatory responses and tissue regeneration. Therefore, precisely targeting macrophages and activating their anti-inflammatory functions could serve as an effective strategy for alleviating ulcerative colitis. MATERIALS AND METHODS: We propose a novel rosiglitazone-phosphatidylserine composite nanoparticle (PLN-PSR). Through precipitation-self-assembly synthesis, the polymer-lipid hybrid nanoparticle externalizes phosphatidylserine, which serves as an "Eat Me" signal. This signal is captured by macrophage receptors, triggering phagocytosis and prompting macrophages to scavenge inflamed tissue areas. Simultaneously, the nanoparticle releases the encapsulated rosiglitazone, which alleviates inflammatory responses in colonic tissue via the proliferator-activated receptor gamma (PPAR-γ) pathway. RESULTS: PLN-PSR showed good stability and biocompatibility, targeted macrophages in inflamed colon, alleviated dextran sulfate sodium (DSS)-induced colitis, and promoted M1-to-M2 macrophage polarization. CONCLUSIONS: PLN-PSR enables targeted anti-inflammatory delivery via macrophage phagocytosis and modulates macrophage function, representing a promising UC therapy.