Abstract
Pseudomyxoma peritonei (PMP) is difficult to treat. Intraperitoneal delivery of mucolytic solutions might potentially improve therapy, in addition to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy. Comparison of mucolytic effect of two formulations (control: bromelain 300 µg/mL+N-Acetylcystein 250 mM; test: bromelain 200 µg/mL+200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Mucin plugs were classified according to their density into three categories: hard, semi hard and soft. Simulation of peritoneal washing ex vivo using a closed heated circulating pump. Solubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p < 0.05). The test solution was also more effective in dissolving the hard mucus plugs compared to control (82.5±2.74 % vs. 36.33±3.27 %). All mucin types disintegrated in simulated peritoneal washing. Cytotoxicity of the test solution on HT29 cell line was time-dependent. The test formulation is more effective and faster than the control formulation in dissolving mucus plugs of various densities. Mucus plugs were all solubilised after 40 min in simulated peritoneal washing. This novel mucolytic formulation might pave the way for an effective and less invasive therapy of PMP in the future.
Highlights
Comparison of mucolytic effect of two formulations in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 Pseudomyxoma peritonei (PMP) patients
Solubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p < 0.05)
Simultation study: Peritoneal wash simulation to disintegrate PMP mucin with 50 μg/mL bromelain + 50 mM cysteamine: A mass of 5 g of mucin from each mucin grade was deposited into a 400 mL beaker that has an inflowing and out flowing polypropylene tube and containing either 200 mL of Tris buffer, 200 mL of Tris with 50 μg/mL bromelain, 200 mL of Tris with 50 μg/mL cysteamine or 200 mL Tris containing 50 μg/mL bromelain + 50 mM cysteamine
Summary
Methods: Comparison of mucolytic effect of two formulations (control: bromelain 300 μg/mL + N-Acetylcystein 250 mM; test: bromelain 200 μg/mL + 200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Results: Solubilisation was faster with the test vs the control formulation (90 vs 180 min) for dissolving the soft mucin plugs (p < 0.05). Conclusions: The test formulation is more effective and faster than the control formulation in dissolving mucus plugs of various densities. Mucus plugs were all solubilised after 40 min in simulated peritoneal washing. This novel mucolytic formulation might pave the way for an effective and less invasive therapy of PMP in the future
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