The aim of this study was to develop a novel biodegradable polymeric carrier for the delivery of protein vaccine orally in order to target the antigen presenting cells (APCs) in the region of Peyer's patches (PPs). Here, bovine serum albumin (BSA) was chosen as a model protein vaccine and was loaded into the mannosylated chitosan nanoparticles (MCS NPs) by ionic gelation method with tripolyphosphate (TPP), followed by coating MCS NPs with Eudragit® L100 (Eud) by electrostatic interaction. The spherical NPs were successfully prepared with appropriate particle size around 558.2 ± 35.6 nm, high entrapment efficiency about 90.38 ± 9.12%, good stability and reasonable release behavior in the simulated gastrointestinal fluid, meanwhile high resistance of enzymatic and acid degradations were verified. The targeting ability of the NPs to PPs in rat was investigated by a closed ileal loop assay, where fluorescence visualization was performed. MCS NPs were accumulated more specifically into PPs after Eudragit® L100 dissolved in intestinal juices. Oral immunization using BSA-loaded Eudragit® L100-coated MCS NPs was found to elicit strong systemic IgG antibody and mucosal IgA responses. These results suggested that enteric-coated MCS NPs could serve as a promising carrier for oral protein vaccine delivery.
Pyroptosis is involved in various inflammatory and fibrotic processes, but its specific role in the progression of chronic pancreatitis (CP) remains insufficiently explored. This study first investigated the dynamic expression changes of pyroptosis-related proteins during CP development and verified the regulatory effects of disulfiram (DSF) on key effector cells in CP, namely pancreatic stellate cells (PSCs) and macrophages. Building on these findings, a gut microenvironment-responsive nanoplatform, CuSe/DSF/EL nanoflowers, was designed and synthesized by integrating CuSe (as a carrier and selenium donor), DSF (as the core therapeutic agent), and Eudragit ® L100-55 (EL, a pH-sensitive polymer for intestinal targeting). Results demonstrated that the CuSe/DSF/EL nanoflowers exhibited excellent biocompatibility, robust antioxidant capacity, and efficient electrostatic targeting to inflamed pancreatic tissues via charge interactions. In vivo experiments using a mouse CP model confirmed that the nanoflowers significantly alleviated pancreatic inflammation, fibrosis, and pyroptosis, while effectively repairing pancreatic structure and restoring its function. Further RNA sequencing (RNA-seq) analysis revealed that the nanoflowers reversed CP-associated transcriptomic dysregulation, with a notable focus on correcting impaired pancreatic secretion pathways. This study clarifies the critical role of pyroptosis in CP pathogenesis and provides a novel, multi-mechanistic nanotherapeutic strategy for CP treatment by enhancing the bioavailability and targeting efficiency of DSF.
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