# Treating Peritoneal Malignancies with Paclitaxel-Loaded Expansile Nanoparticles

> **NIH NIH R44** · IONIC PHARMACEUTICALS · 2020 · $1,017,202

## Abstract

ABSTRACT
A primary challenge in the treatment of peritoneal malignancies, such as intraperitoneal mesothelioma and
ovarian cancer, is preventing tumor recurrence in patients following the surgical removal of tumor (5-year survival
<15% and <45%, respectively). Intraperitoneal administration of chemotherapy (e.g., paclitaxel) has been shown
clinically to improve patient outcomes and prevent local tumor recurrence (the principal deterrent to long-term
survival). However, despite these modest improvements, there are significant limitations to this therapy. For
example, the current clinical formulation of paclitaxel (i.e., Taxol®) is: A) limited due to toxic side effects resulting
from absorption across the entire surface of the peritoneal cavity with no mechanism for tumor specificity; and,
B) rapidly cleared from the peritoneal cavity (<10% remaining after 6 hours) resulting quickly in sub-therapeutic
drug levels within the tumor tissue. The proposed project develops a novel, patented, technology, the expansile
nanoparticle (eNP), designed to address these challenges and to target the primary observable cause of patient
relapse (locally recurrent peritoneal tumors). eNPs decrease toxicity and increase efficacy via: a) unique
Materials-Based Targeting, which leads to preferential and prolonged accumulation in tumors; and, b) triggered
drug release following particle swelling, which occurs in response to exposure to lowered pH (5-6.5) found in the
tumor microenvironment or in the endosomes of tumor cells. The results of our Phase I SBIR project include: 1)
a radiolabeled biodistribution study demonstrating up to 65% of the injected dose of paclitaxel-loaded-eNPs
(PTX-eNPs) accumulates in tumors via Materials-based Targeting, without the need for targeting ligands, and
localization persists for up to 2 weeks; 2) PTX-eNPs deliver 10- to 100-fold higher intratumoral
concentrations of paclitaxel than Taxol over a seven day period following injection; 3) PTX-eNPs reduce the
amount of recurrent ovarian tumor by 3-fold (v. Taxol) and more than double survival (v. Taxol) in an orthotopic,
multiple-dose, treatment of intraperitoneal mesothelioma model; and, 4) successful PTX-eNP production on
the liter scale. This proposal addresses four activities on the critical path to obtaining an active IND application
to evaluate PTX-eNPs in a Phase I clinical trial, including: Aim 1) Transfer of production processes and analytical
methods for the eNP polymer to Norac Pharma (a contract manufacturing organization; CMO) followed by
optimization of a scalable method and production of 1-2 kg of eNP polymer material; Aim 2) Transfer of
production processes for the PTX-eNP to Particle Sciences (CMO) followed by optimization of a large-scale
manufacturing method, production of PTX-eNPs for use in Aim 3 & 4 in vivo studies, development of analytics
and stability testing; Aim 3) Perform a dose-escalation to determine the NOAEL and toxicity testing under current
Good Laboratory ...

## Key facts

- **NIH application ID:** 9952341
- **Project number:** 5R44CA189215-03
- **Recipient organization:** IONIC PHARMACEUTICALS
- **Principal Investigator:** Aaron Henry Colby
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,017,202
- **Award type:** 5
- **Project period:** 2014-09-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952341

## Citation

> US National Institutes of Health, RePORTER application 9952341, Treating Peritoneal Malignancies with Paclitaxel-Loaded Expansile Nanoparticles (5R44CA189215-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9952341. Licensed CC0.

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