Comparative in vitro evaluation of microspherical embolisation agents.

This study describes the comparative performance of four commercially available microspherical embolisation products: Embosphere, Embogold, Contour SE and Bead Block. A series of in vitro evaluations were designed to assess the mechanical and biological characteristics of these biomaterials. Size distribution analysis revealed sieving techniques used to fractionate the embolics produced similar size distributions. The forces required to compress Embosphere, Embogold and Bead Block were in the range 21-27.5 kPa. Contour SE was significantly more compressible at approximately 5 kPa. However, recoverability of Contour SE required several minutes in contrast to the other products, a phenomenon attributed to its macroporous structure. When time taken to reach and remain in suspension was studied, results showed that the products quickly reached equilibrium with contrast agent. Bead Block was maintained in suspension for twice as long as the other products. Catheter deliverability was assessed and found to be dependent upon both microsphere and catheter, the best combination being Bead Block delivered via the Progreat catheter. Both the blood contacting SEM and plasma coagulation time showed none of the products were pro-thrombic or pro-coagulatory, each producing comparable results. Small differences in physical properties such as compressibility, could play an important role in delivery and effectiveness of vessel blockage. Currently all products are used routinely in clinical practice.

DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization.

PURPOSE: The purpose of this investigation is to present the in vitro characterization and detailed drug-loading procedure for DC Bead, a microsphere product that can be loaded with chemotherapeutic agents for embolization. MATERIALS AND METHODS: DC Bead is an embolic microsphere product that is capable of being loaded with anthracycline drugs such as doxorubicin just before administration in a transarterial chemoembolization (TACE) procedure. Beads can be loaded from solutions prepared from doxorubicin powder or the doxorubicin HCl formulation. In this evaluation, bead sizes were measured by optical microscopy with video imaging. Gravimetric analysis demonstrated the effect of drug loading on bead water content, and its consequent impact on bead compressibility was determined. The subsequent deliverability of the beads was assessed by mixing the beads with contrast medium and saline solution and passing the beads through an appropriately sized microcatheter. A T-cell apparatus was used to monitor the in vitro elution of the drug from the beads over a period of 24 hours in various elution media. RESULTS: DC Bead spheres could be easily loaded with doxorubicin to a recommended level of 25 mg/mL of hydrated beads by immersion of the beads in the drug solution for 10-120 minutes depending on microsphere size. Other commercial embolic microspheres were shown not to load doxorubicin to the same extent or release it in the same fashion and were considered unsuitable for local drug delivery. Maximum theoretic capacity for DC Bead was approximately 45 mg/mL. Increase in doxorubicin loading resulted in a concomitant decrease in water content and consequential increase in bead resistance to compression force. Drug loading also resulted in a decrease in the average size of the beads, which was dependent on bead size and drug dose. This did not impact bead delivery at any drug loading level to a maximum of 37.5 mg/mL. Beads 100-700 microm in size could be delivered through 2.7-F microcatheters, whereas the 700-900-microm range required 3-F catheters. Modeling of the kinetics of drug elution from the beads in vitro at a loading dose of 25 mg/mL yielded calculated half-lives of 150 hours for the 100-300-microm range to a maximum of 1,730 hours for the 700-900-microm size range, which was dependent on the ionic strength of the elution medium. For comparison, there was a rapid loss of drug from an unstable Lipiodol emulsion with a half-life of approximately 1 hour. CONCLUSIONS: DC Bead can be loaded with doxorubicin to provide an accurate dosage of drug per unit volume of beads. Drug elution is dependent on ion exchange with the surrounding environment and is controlled and sustained, unlike the rapid separation of the drug from Lipiodol. Drug loading has no impact on the handling and deliverability of the beads, making them suitable for superselective TACE.

Biological evaluation and drug delivery application of cationically modified phospholipid polymers.

Phospholipid-like polymers based on 2-methacryloyloxyethyl phosphorylcholine containing varying amounts of the cationically charged monomer choline methacrylate (CMA) from 0 to 30 wt% have been prepared. Substrates coated with these materials were shown to bind significantly lower amounts of specific proteins compared to the uncoated control. ELISA assays demonstrated that fibrinogen did not bind appreciably to coatings containing 0-30% CMA, whereas albumin binding was seen to increase significantly as the CMA content of the coating increased. Platelet activation assays, measurement of plasma coagulation time and whole blood contact scanning electron micrography demonstrated that the haemocompatibility of the coatings was shown to be unaffected by the CMA component. The CMA polymer coatings have been shown to absorb/adsorb many different drug compounds covering a wide range of molecular weights and release these in a controlled fashion. The range of cationic polymers assessed can interact with the net negative charge found in many large therapeutic biomolecules, such as DNA fragments used in gene therapy, that may be of interest in the preventative treatment of conditions such as restenosis. Coronary stents coated with 6% or 20% CMA-containing polymers have been shown to load and release this type of genetic material irrespective of molecular weight of the biomolecule. Ex vivo and in vivo studies have shown that these compounds can be delivered to the stented section of the vessel with very low quantities delivered outside the vessel target area.