Beading cancer - localised tumour treatment

Materials World magazine
,
24 Jul 2012
Doxorubicin-loaded DC Bead

As the battle against cancer continues, the use of polymer beads to enable localised treatment of tumours is proving beneficial to patients and physicians alike. All hail the DC Bead, says Andy Lewis, Director of Research and Development at Biocompatibles UK Ltd.  

The fight against cancer has advanced beyond the conventional infusion of chemotherapy cocktails, to include a host of approaches designed to enable site-specific treatment of solid tumours. From radiation-impregnated devices such as titanium seeds and glass-resin microspheres for selective internal radiation therapy, to biomedical polymer systems for localised delivery and sustained release of highly toxic drugs, harnessing the materials-drug interface has never been more important. 

The key to the success of such an approach is the ability to specifically target the cancer, maximise the therapeutic effect and minimise the systemic toxicity. As such, many of these systems are administered by minimally invasive interventions, with the aid of sophisticated image-guidance techniques to ensure the devices are localised within the tumour. Imaging techniques such as X-ray computed tomography (CT) are used to diagnose the existence and location of a tumour and its response following treatment. 

Take the example of a liver tumour. Once the tumour has been identified, the patient is taken to a catheterisation laboratory where the appropriate therapy can be administered. This is commonly performed under the guidance of real-time imaging using low-energy X-ray fluoroscopy to generate an arteriogram – a map of the arterial blood supply to the liver. Embolotherapy represents such an image-guided approach, whereby a microcatheter is steered into position within the main arteries feeding a tumour, followed by administration of embolisation agents to block its blood supply.

 

Targeting the tumour 

DC Bead consists of polymer beads with a chemical structure that enables them to actively sequester certain drugs rapidly and efficiently from a solution. A simple immersion process in the hospital pharmacy loads the beads with the appropriate drug dose prior to use. Bead size is selected according to vascularity of the tumour, and the beads are then delivered directly into the tumour blood vessels where they occlude blood flow, depriving the cancer of nutrients and oxygen. Once lodged in the tumour, the beads deliver a high, local dose of chemotherapy over a sustained period of time. 

Pharmacokinetic studies in patients treated with DC Bead have demonstrated significant reductions in chemotherapy blood levels and, consequently, fewer adverse systemic side effects such as alopecia, when compared with the conventional liver cancer treatment of transcatheter arterial chemoembolisation (TACE). Tumour response rates are also improved, particularly in patients with advanced stages of the disease who are more difficult to treat. Moreover, the localised application of these drug-eluting beads is also being evaluated beyond the setting of embolisation in the treatment of glioblastoma multiforme and pancreatic cancer, by injection of the tumour resection margin or direct intratumoural injection of the beads. 

Life through a lens 

The material from which the product is derived is based on a hydrogel polymer originally developed for soft contact lens applications. The chemical structure is composed largely of water-soluble polyvinyl alcohol (PVA) that has been modified to form a reactive macromonomer. This is copolymerised with 2-acrylamido-2-methylpropanesulfonate sodium salt (AMPS – a monomer used in the preparation of a range of materials for biomedical applications) using a reverse suspension polymerisation to form microspheres. These are subsequently dyed blue to aid in their visualisation and handling, and then mechanically sieved into a range of sizes. 

The hydrogel structure consists of a swollen network of hydrophilic polymer chains composed of around 95% water by weight. One of the materials challenges faced when developing this device was in forming a high water-content system with sufficient mechanical integrity to enable compression during delivery through narrow lumen catheters, while avoiding fragmentation and allowing for rapid elastic recovery of the shape. Moreover, the AMPS provides an abundance of sulfonic acid groups, which give the added benefit of ion-exchange between the sodium counterions and other positively charged ions in the solution in which the beads are immersed. 

When the solution contains a suitably charged drug, such as doxorubicin hydrochloride, the drug diffuses into the structure, displaces the sodium ions and, through electrostatic interactions, binds to the sulfonate groups. This property means DC Bead can be provided to a physician in an unloaded state, allowing the choice and dose of drug to be selected and loaded prior to use. Once inside the body, release of the drug is kept slow and sustained through the reverse process of exchange with ionic constituents in the tissue fluids. 

At present, DC Bead is used in over 50 different countries worldwide and has been used to treat more than 100,000 patients. Through harnessing the materials-drug interface, this innovative biomedical polymer product delivers the benefits of both consistency and ease of use. Since its introduction into standard patient care, it has significantly improved patient tolerance of the cancer treatment procedure, with enhanced outcomes and improved quality of life for patients.