# Application of mucus modulating multipurpose bromelain nanoparticles to overcome the mucus barrier in appendiceal pseudomyxoma peritonei

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $216,626

## Abstract

PROJECT ABSTRACT
Pseudomyxoma peritonei (PMP), an insidious but lethal malignancy, refers to peritoneal metastases from
appendix mucinous neoplasms (AMN). PMP is characterized by abundant extracellular mucus that accumulates
in the abdominal cavity and forms a protective barrier around cancer cells, hindering chemotherapeutic drug
delivery. We hypothesize that destruction (mucolysis) and/or modulation (disruption) of extracellular mucus
structure is a promising therapeutic strategy to overcome the protective mucus barrier posed by extracellular
mucus in PMP, enabling chemotherapeutic drug delivery. In our prior research we utilized patient derived
xenograft (PDX) models of PMP in order to demonstrate that intraperitoneal (IP) administration of a novel
combination of mucolytic drugs, bromelain (BRO; a cysteine protease) and N-acetylcysteine (NAC, a reducing
agent that breaks disulfide bonds), successfully dissolves extracellular mucus (mucolysis) and enhances
chemotherapeutic drug delivery to cancer cells. The aim of this proposal is to leverage nanotechnology to
enhance IP retention time and intratumoral (IT) penetration by BRO+NAC in order to optimize mucolysis and
chemotherapeutic drug delivery in PMP. To this end, we have generated preliminary data demonstrating that it
is possible to successfully engineer mucus modulating multipurpose BRO nanoparticles (MBN) comprised of
four components; (a) a BRO nanoparticle core, for enzymatic mucolysis; (b) conjugated L-cysteine, for
mucoadhesion through disulfide bond formation; (c) conjugated NAC, for mucus disruption through reduction of
disulfide bonds; and (d) conjugated doxorubicin (DOX), for cancer therapy. In addition, we have also successfully
synthesized iron oxide nanoparticle clusters coated with hydrogen ions and glutathione (INC-H+G), for co-
delivery with our MBN, to increase the reduction potential of mucus and enhance the function of the MBN. The
specific aims of this research proposal are to (a) assess the ability of MBN to modulate mucus structure and
enhance chemotherapeutic drug delivery using patient-derived in vitro models of PMP; and (b) observe the effect
of MBN on mucinous tumor growth in PDX models of PMP. We expect to demonstrate that the proposed
MBN will provide a pharmacokinetic and pharmacodynamic advantage over free mucolytic/cytotoxic
drugs. Notably, the proposed MBN are also synthesized from biocompatible and biodegradable materials,
increasing the translatability of the approach. We are uniquely positioned to conduct the preclinical studies in
this proposal given that we have already developed the proposed in vitro and in vivo models of AMN/PMP in our
own laboratory and our institution is one of the major international referral centers for the management of patients
with PMP.

## Key facts

- **NIH application ID:** 10457440
- **Project number:** 5R21CA263468-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mohammad Haroon Asif Choudry
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $216,626
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457440

## Citation

> US National Institutes of Health, RePORTER application 10457440, Application of mucus modulating multipurpose bromelain nanoparticles to overcome the mucus barrier in appendiceal pseudomyxoma peritonei (5R21CA263468-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10457440. Licensed CC0.

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