Tumour-penetrating microparticles (TPM), drug delivery vehicles that have been designed to specifically target and infiltrate
peritoneal tumours, are more efficacious than standard chemotherapy, according to our preliminary research data.1
The peritoneal cavity contains organs, such as the pancreas, liver, colon and ovary, that are responsible for a large portion
of cancer deaths. Pancreatic cancer cells, for example, are surrounded by a specialized network of cells and proteins that
present the biggest hurdle to chemotherapeutic delivery, and hence treatment success. Our goal was to develop a drug delivery
system that would effectively target and penetrate these barriers and deliver drug directly to the cancer cells.
How does it work?
Specifically, TPM is paclitaxelloaded poly(lactide-co-glycolide) microparticles with several features that improve the targeting
of tumours in the intraperitoneal and retroperitoneal cavity, including:
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Size: The average size of TPM (5 µm) is optimized to limit clearance from the peritoneal cavity, and to enable wide distribution
in the cavity and penetration into tumours.
- Polymer properties: TPM selectively adheres to the tumour surface.
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Multifunctional delivery system: TPM comprises two components of paclitaxel-loaded particles. One component provides rapid drug release to induce tumour priming
(a technology that uses paclitaxel to transiently expand the interstitial space, and is tumour-selective because of the greater
susceptibility of tumour cells to drug-induced apoptosis compared with normal cells). The tumour priming feature of TPM enables
the drug/particles to penetrate the inner layers of tumours. The second component of the delivery system releases the remainder
of the dose slowly over the course of several weeks. This twotiered drug attack is unique in pancreatic cancer treatment.
The collective properties of TPM result in tumour-selective delivery, reduced drug exposure in normal tissues, and control
of rapidly and slowly growing tumours.
According to our research, one dose of TPM, administered intraperitoneally, is as effective as multiple injections of chemotherapy;
it is present in the peritoneal lavage for at least 1 week2 and for at least 4 weeks in peritoneal tumours.3 The delivery system is specifically tailored to the unique anatomical properties of the abdominal cavity, targets the tumours
and releases the drug contents at pharmacodynamically optimized rates. This fractionated dose presentation reduces the local
toxicity whilst eliminating the need for repeated catheterization.
In practice
Multiple clinical trials have shown that instilling a drug solution directly into the peritoneal cavity can effectively treat
tumours originating from organs in the peritoneal cavity, such as ovarian cancer. This mode of administration, however, poses
two limitations that have prevented its widespread use, despite its demonstrated efficacy: local toxicity and inability of
the drug to penetrate bulky tumours. TPM is designed to overcome these limitations, and represents a delivery platform that
can be used to deliver small molecule therapeutics, biologics, gene vectors and imaging agents directly to peritoneal tumours.
We have been working on TPM for more than 10 years now and we anticipate approval from the FDA to take our candidate into
clinical trials this year.
References
1. J.L-S. Au, et al., "Tumor penetrating microparticles for intraperitoneal treatment of pancreatic cancer," presented at the 2009 American Association
of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition (Los Angeles, CA, USA, 8–12 November 2009).
2. M. Tsai, et al., Pharm. Res., 24(9), 1691–1701 (2007).
3. Z. Lu et al., J. Pharmacol. Exp. Ther.,
327(3), 673–682 (2008).
Professor Au's research was presented at the 2009 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting
and Exposition, 8–12 November 2009, Los Angeles, USA.
Professor Au is co-founder of Optimum Therapeutics LLC, the company hoping to take TPM to clinical trials.
