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Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct of polyethylene glycol (PEG), (PEG–BA), on PC cells (MIA PaCa-2), a normal cell line (Vero) and on peripheral blood mononuclear cells (PBMCs). PEG–BA, was tested for its effect on cell death, immunomodulation and chemoresistance-linked signalling pathways. The conjugate was significantly more toxic to PC cells (p < 0.001, IC50 of 1.35 ± 0.11 µM) compared to BA (IC50 of 12.70 ± 0.34 µM), with a selectivity index (SI) of 7.28 compared to 1.4 in Vero cells. Cytotoxicity was confirmed by increased apoptotic cell death. PEG–BA inhibited the production of IL-6 by 4–5.5 fold compared to BA-treated cells. Furthermore, PEG–BA treatment of MIA PaCa-2 cells resulted in the dysregulation of crucial chemoresistance genes such as WNT3A, TXNRD1, SLC2A1 and GATA3. The dysregulation of chemoresistance-associated genes and the inhibition of cytokines such as IL-6 by the model polymer construct, PEG–BA, holds promise for further exploration in PC treatment.

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Objectives: Interleukin (IL)-21 is a cytokine associated with tissue inflammation, autoimmune and infectious diseases. Organ dysfunction and death can occur in patients with acute pancreatitis in two distinct clinical phases. Initially, a systemic inflammatory response syndrome which may be followed by systemic sepsis from infected pancreatic necrosis, known as the 'second hit'. The expression and possible role of IL-21 in acute pancreatitis has not been established. Methods: Thirty-six patients with mild, moderate and severe acute pancreatitis were enrolled. Peripheral blood samples of patients were drawn on days 7, 9, 11, and 13. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine the expression and concentration of IL-21. Results: Interleukin-21 mRNA levels increased significantly at day 9 in severe (P = 0.002) pancreatitis compared to both the mild and control patient groups. At the protein level, IL-21 was elevated in severe acute pancreatitis patients compared to mild, although this was not significant. Furthermore, day 9 IL-21 was elevated in septic severe acute pancreatitis patients and patients with pancreatic necrosis. Conclusions: Interleukin-21 is transiently elevated in severe acute pancreatitis compared to the mild/moderate group and hence IL-21 may contribute to the immune imbalance that occurs in acute pancreatitis.