Composition-property relationships for radiopaque composite materials: pre-loaded drug-eluting beads for transarterial chemoembolization

Abstract

The purpose of this study was to synthesize and optimize intrinsically radiopaque composite embolic microspheres for sustained release of doxorubicin in drug-eluting bead transarterial chemoembolization. Using a design of experiments approach, 12 radiopaque composites composed of polylactic-co-glycolic acid and a radiopaque glass (ORP5) were screened over a range of compositions and examined for radiopacity (computed tomography) and density. In vitro cell viability was determined using an extract assay derived from each composition against the human hepatocellular carcinoma cell line, HepG2. Mathematical models based on a D-Optimal response surface methodology were used to determine the preferred radiopaque composite. The resulting radiopaque composite was validated and subsequently loaded with doxorubicin between 0 and 1.4% (wt% of polylactic-co-glycolic acid) to yield radiopaque composite drug-eluting beads. Thereafter, the radiopaque composite drug-eluting beads were subjected to an elution study (up to 168 h) to determine doxorubicin release profiles (UV-Vis spectroscopy) and in vitro cell viability. Radiopaque composites evaluated for screening purposes had densities between 1.28 and 1.67 g.cm(-3), radiopacity ranged between 211 and 1450HU and cell viabilities between 91 and 106% were observed. The optimized radiopaque composite comprised 23 wt% polylactic-co-glycolic acid and 60 wt% ORP5 with a corresponding density of 1.63 ± 0.001 g.cm(-3), radiopacity at 1930 ± 44HU and cell viability of 89 ± 7.6%. Radiopaque composite drug-eluting beads provided sustained doxorubicin release over 168 h. In conclusion, the mathematical models allowed for the identification and synthesis of a unique radiopaque composite. The optimized radiopaque composite had similar density and cell viability to commercially available embolic microspheres. It was possible to preload doxorubicin into radiopaque composite drug-eluting beads, such that sustained release was possible under simulated physiological conditions.

Updates of colorectal cancer liver metastases therapy: review on DEBIRI

“…Recent improvements of TACE, including the introduction of new types of embolics (PEG microspheres), have increased tumor response in CRC-LM patients [23,24]. Some type of beads (LUMI) incorporate an imaging agent and can be loaded with a chemotherapeutic drug and can be visualized during TACE and in follow-up imaging [25][26][27].…”

“…In the past decade, several efforts have been made to improve TACE tolerability, including drug dosage adjustments, incremental experience of interventional radiologist, introduction of new type of drugs and microspheres to obtain a more precise and selective treatment [23][24][25][26][27].…”

Stimulation of apoptotic pathways in liver cancer cells: An alternative perspective on the biocompatibility and the utility of biomedical glasses

“…suggest that radiopacity values comparable to those obtained herein may provide a method to evaluate the spatial distribution of particles using either cone beam CT immediately postembolization or with conventional CT scan during follow-up. 54 Using mice, Meng et al. show that subcutaneously implanted microspheres with radiopacity values approximately equal to 4250 HU were visible using X-ray.…”

“…Nevertheless, Kilcup et al suggest that radiopacity values comparable to those obtained herein may provide a method to evaluate the spatial distribution of particles using either cone beam CT immediately postembolization or with conventional CT scan during follow-up. 54 Using mice, Meng et al show that subcutaneously implanted microspheres with radiopacity values approximately equal to 4250 HU were visible using X-ray. 55 Lee et al demonstrated that tantalum containing nanoparticles with radiopacity values below 1000 HU when suspended in water caused enhanced visibility of blood vessels, spleen, and liver in a rat using CT imaging.…”

Radiopaque and uniform alginate microspheres loaded with tantalum nanoparticles for real-time imaging during transcatheter arterial embolization

“…Several groups have investigated such radiopaque DEBs. For example, 2,3,5-triiodobenzaldehyde has been coupled to the backbone of polyvinyl alcohol to produce DC Bead LUMI 17 - 20 , whereas radiopaque composites of poly lactic-co-glycolic acid and a radiopaque glass have also been produced 21 . However, the synthesis of such copolymers or radiopaque glass is rather complicated, and so there is need for a universal method to economically and easily produce radiopaque DEBs from readily available materials.…”