Doxorubicin eluting beads - 1: effects of drug loading on bead characteristics and drug distribution.
DC Bead is a FDA cleared embolisation device for the treatment of hypervascular tumours and arteriovenous malformations. This product is currently evaluated in a number of centres in Europe as an embolic device for transarterial chemoembolisation (TACE). The beads consist of poly(vinyl alcohol) microspheres modified with sulfonic acid groups and are available at different size ranges varying from 100 to 900 microm in diameter. The beads were shown to actively sequester doxorubicin hydrochloride (dox) from solution in a time dependent upon the dose of the drug and size of the beads. Drug uptake was by an ion-exchange mechanism, and in the absence of other ions in solution, the beads could load a maximum of around 40 mg dox/mL hydrated beads, with >99% of drug being sequestered from the solution. A loading of 25 mg dox/mL beads was recommended as providing a practical therapeutic dose and optimum handling characteristics. There was a decrease in equilibrium water content of the beads with increasing dox loading, which resulted in a decrease in the average diameter of the beads and an increase in the compressive modulus. The deliverability properties, however, were not affected after drug loading. Using a variety of microscopic methods, the drug was shown to be distributed throughout the bead structure, but concentrated in the outer 20 microm surface layer, a feature related to the method of synthesis. This study characterises the properties of DC Bead loaded with dox with respect to important characteristics in embolisation and demonstrates the potential of this drug device combination for the treatment of hypervascular tumours such as hepatocellular carcinoma.
Lewis
Andrew L
AL
Drug Delivery Division, Biocompatibles UK Ltd, Farnham Business Park, Farnham, Surrey, UK. andrew.lewis@biocompatibles.com
Gonzalez
M Victoria
MV
Leppard
Simon W
SW
Brown
Joanna E
JE
Stratford
Peter W
PW
Phillips
Gary J
GJ
Lloyd
Andrew W
AW
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy; D016461:Chemoembolization, Therapeutic; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006499:Hepatic Artery; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011142:Polyvinyl Alcohol
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004317:Doxorubicin; D011142:Polyvinyl Alcohol