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:
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.
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.
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.