A Formulation for in Situ Lysis of Mucin Secreted in Pseudomyxoma Peritonei

Int J Cancer. 2014 Jan 15;134(2):478-86. doi: 10.1002/ijc.28380. Epub 2013 Aug 7.

Abstract

Although numerous clinical attempts have been made to disintegrate mucin secreted by pseudomyxoma peritonei (PMP), none are clinically recommended. Through examination of the pharmacologic characteristics of two novel agents, we titrated an optimized combination of bromelain and N-acetyl cysteine (NAC) that demonstrates in vitro and in vivo efficacy in the dissolution of mucinous ascites from PMP. In the in vitro experiments, 1 g of mucin was incubated in varying concentrations of bromelain (0-400 µg/ml) and NAC (0-5%) individually followed by a combination before arriving at a therapeutic combination dose of 300 µg/ml bromelain+4% NAC. This established an effective dose of bromelain 300 µg/ml+4% NAC at pH 7.0, when tested in a rat model implanted with 3 g of mucin intraperitoneally (IP). IP administration of the drug in a rat model of PMP was shown to result in mucin disintegration within 72 hr with no toxicity observed.

Keywords: cytoreductive surgery; mucinous ascites; mucolysis; peritoneal metastases; pseudomyxoma peritonei.

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Bromelains / pharmacology*
  • Drug Combinations
  • Expectorants / pharmacology*
  • Male
  • Mucins / metabolism*
  • Mucus / drug effects
  • Mucus / metabolism*
  • Peritoneal Neoplasms / drug therapy*
  • Pseudomyxoma Peritonei / drug therapy*
  • Rats
  • Rats, Nude

Substances

  • Drug Combinations
  • Expectorants
  • Mucins
  • Bromelains
  • Acetylcysteine