Nanotherapy for acute pancreatitis: a systematic review of experimental strategies and mechanisms of action

BACKGROUND: Acute pancreatitis (AP) is a severe inflammatory disease that has limited pharmacological options. Nanotechnology-based drug delivery systems have shown promise in preclinical models, but a comprehensive synthesis of their mechanisms and therapeutic profiles in AP is lacking. OBJECTIVE: To systematically review preclinical nanotechnology-based therapeutic strategies for acute pancreatitis and to classify nanocarriers according to their dominant mechanisms of action. METHODS: We systematically searched PubMed, Scopus, and Google Scholar for studies using on in vivo AP models treated with nanomaterials or nanoformulations. Eligible studies have reported therapeutic outcomes compared with non-nano or untreated controls. RESULTS: Fifty-six in vivo studies met our inclusion criteria. Most investigated polymeric (PLGA, PEG-PLGA, and silk fibroin) and lipid-based nanocarriers have fewer inorganic/metal-based and biological or biogenic nanostructures. Across heterogeneous AP models, nanoformulations consistently reduced pancreatic edema, necrosis, and inflammatory infiltrates; lowered serum amylase/lipase and pro-inflammatory cytokines; attenuated remote organ injury, particularly acute lung injury, relative to controls; and improved survival in severe AP. Mechanistically, nanotherapeutics chiefly exert anti-inflammatory and antioxidant effects, often accompanied by modulation of calcium overload, mitochondrial dysfunction, cell death, and microcirculatory disturbances. CONCLUSIONS: Preclinical evidence indicates that nanotechnology-based interventions can ameliorate pancreatic and systemic injury in experimental AP through multitarget modulation of key pathogenic pathways. Nevertheless, the heterogeneity of models and nanoplatforms, limited safety data, and substantial risk of bias preclude firm conclusions about comparative efficacy or clinical applicability. More rigorous and standardized preclinical studies, along with carefully designed translational research, are needed to identify nanotherapeutic strategies suitable for future clinical testing in AP.