Assessment of a novel mucolytic solution for dissolving mucus in pseudomyxoma peritonei: an ex vivo and in vitro study

Abstract

Background: 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. 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. 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. Results: 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. 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.

Mucinous appendiceal neoplasms with or without pseudomyxoma peritonei: a review

“…12 Mucolytic therapies such as the combination of Bromelain and N-acetylcysteine administered through radiologically placed catheters could potentially be more effective at decreasing jelly-type tumour burden in inoperable patients and human studies are underway. 38 In conclusion, appendiceal mucinous neoplasms are a very complicated group of tumours to manage, in part because of ongoing issues with the classification and nomenclature of these tumours. Every general surgeon should have a sound understanding of the clinical and pathological nuances used in the treatment algorithm of MANs.…”

“…They generally follow a rather benign course with recurrent disease, often necessitating debulking surgery or palliative procedures for malignant bowel obstruction 12 . Mucolytic therapies such as the combination of Bromelain and N‐acetylcysteine administered through radiologically placed catheters could potentially be more effective at decreasing jelly‐type tumour burden in inoperable patients and human studies are underway 38 …”

The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2

“…The recently emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID- 19), which can range from asymptomatic to severe and lethal forms with a systemic inflammatory response syndrome. As of 21 February 2021, over 111 million confirmed cases have been reported, with an estimated overall mortality of 2.2% [1].…”

The combination of Bromelain and Acetylcysteine (BromAc) synergistically inactivates SARS-CoV-2

“…Most importantly, Acetylcysteine reduces disulfide bonds (9). The combination of Bromelain with Acetylcysteine (BromAc) exhibits a synergistic mucolytic effect to treat mucinous tumors (10,11) and as a chemosensitizer of several anticancer drugs (12). These different actions are due to the ability of BromAc to disintegrate molecular structures of complex glycoproteins.…”