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A formulation for in situ lysis of mucin secreted in pseudomyxoma peritonei
Krishna Pillai1, Javed Akhter, Terence C Chua
1UNSW Department of Surgery, St George Clinical School, Kogarah, NSW, Australia.
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.
Insights
A novel combination of bromelain and N-acetyl cysteine (NAC) effectively dissolves mucinous ascites in pseudomyxoma peritonei (PMP). This treatment shows efficacy in vitro and in vivo without observed toxicity in a rat model.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Pseudomyxoma peritonei (PMP) is characterized by mucinous ascites, posing clinical challenges.
- Current clinical strategies for mucin disintegration in PMP lack established recommendations.
Purpose of the Study:
- To identify and optimize a novel therapeutic agent for the dissolution of mucinous ascites in PMP.
- To evaluate the in vitro and in vivo efficacy and safety of a bromelain and N-acetyl cysteine (NAC) combination.
Main Methods:
- In vitro experiments involved incubating mucin with varying concentrations of bromelain and NAC.
- An optimized therapeutic dose was determined: 300 µg/ml bromelain and 4% NAC at pH 7.0.
- In vivo efficacy was tested in a rat model with intraperitoneal mucin implantation.
Main Results:
- The optimized bromelain and NAC combination demonstrated significant mucin dissolution in vitro.
- Intraperitoneal administration in a rat model led to mucin disintegration within 72 hours.
- No observable toxicity was reported in the animal model during the study period.
Conclusions:
- A combination of bromelain and N-acetyl cysteine (NAC) is an effective agent for mucin dissolution in pseudomyxoma peritonei.
- This novel therapeutic approach shows promise for managing mucinous ascites in PMP patients.
- Further clinical investigation is warranted to confirm safety and efficacy in humans.
