An In Vitro Evaluation of Four Types of Drug-Eluting Microspheres Loaded with Doxorubicin

Baère, Thierry De; Plotkin, Stephen; Yu, Renee; Sutter, Allison; Wu, Yuzhang; Cruise, Gregory M.

doi:10.1016/j.jvir.2016.05.015

Cited by 76 publications

(60 citation statements)

References 11 publications

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“…Similarly, the increased ionic nature of Tandem DEB increases the probability of released idarubicin molecules in the medium interacting with the DEB and reabsorbing. Therefore, the reduced rate and quantity of drug elution from Tandem DEB is consistently observed (9,14).…”

Section: Discussionmentioning

confidence: 92%

“…Toward the goal of combining an efficient drug with a drugeluting platform to provide optimal embolization and drug delivery for the treatment of HCC, this study evaluated the in vitro performance of 4 types of DEBs loaded with idarubicin. Regardless of DEB composition, idarubicin is loaded into the hydrogel material through ionizable functional groups, a carboxylate for HepaSphere (11) and Tandem (12) and a sulfonate for DC Bead (13) and LifePearl (9,14) DEBs. The positively charged idarubicin molecules interact with the negatively charged carboxylate or sulfonate groups, replacing the counterions during loading.…”

Section: Discussionmentioning

confidence: 99%

“…This study evaluated 4 brands of DEBs loaded with idarubicin, using the same methods as a recent study evaluating the same 4 DEBs loaded with doxorubicin (9). Both of the studies used the same equipment and methods, permitting a direct comparison of the DEBs with idarubicin and doxorubicin ( Table 3).…”

Section: Idarubicin Loading Elution and Loading Stabilitymentioning

confidence: 99%

“…The present study compared the loading, elution, diameter change, stability, and time in suspension of DC Bead, HepaSphere, LifePearl, and Tandem DEBs loaded with idarubicin. Additionally, this study used the same experimental materials and methods as a recently published study of DEBs and doxorubicin (9), permitting comparisons between the in vitro characteristics of DEBs loaded with idarubicin and those of doxorubicin.…”

mentioning

confidence: 99%

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An In Vitro Evaluation of Four Types of Drug-Eluting Embolics Loaded with Idarubicin

Guiu¹,

Hincapié²,

Thompson³

et al. 2019

Journal of Vascular and Interventional Radiology

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This study compared loading, elution, and stability of drug-eluting embolic beads (DEBs) loaded with idarubicin. Materials and Methods: DC Bead (100-300 μm), HepaSphere (30-60 μm), LifePearl (200 μm), and Tandem (100 μm) DEBs were loaded with 5 mg/mL idarubicin. Loading, elution, diameter changes, loading stability over 2 weeks in storage, and time in suspension were determined for each of the DEBs. Results: Loading of more than 99% of idarubicin was achieved within 15 minutes for LifePearl, DC Bead, and Tandem beads. LifePearl, DC Bead, HepaSphere, and Tandem beads eluted 75% of the total idarubicin released in 13, 24, 42, and 91 minutes, respectively. In vitro elution was completed in 2 hours with 73% ± 3%, 74% ± 3%, 65% ± 6%, and 7% ± 0% of the loaded idarubicin eluted for LifePearl, DC Bead, HepaSphere, and Tandem, respectively. Statistically significant differences were observed at every time point between at least 2 of the products. Overall, in vitro idarubicin elution was rapid and nearly complete for LifePearl, DC Bead, and HepaSphere beads but was minimal and slow from Tandem beads. The average diameter of DEBs after loading was reduced by 5% for LifePearl, whereas it was increased by 9% and 1% for DC Bead and Tandem, respectively. After loading, time in suspension was 11 ± 4 and 10 ± 2 minutes for LifePearl and HepaSphere, respectively, whereas DC Bead and Tandem beads were held in suspension for greater than 20 minutes. Conclusions: Although all 4 DEBs loaded idarubicin within 15 minutes with minimal changes in diameter, the elution amounts, rates of release, and time in suspension varied. ABBREVIATIONS DEB ¼ drug-eluting embolic beads, HCC ¼ hepatocellular carcinoma, HPLC ¼ high-performance liquid chromatography

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Idarubicin Loading Elution and Loading Stabilitymentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

An In Vitro Evaluation of Four Types of Drug-Eluting Embolics Loaded with Idarubicin

Guiu¹,

Hincapié²,

Thompson³

et al. 2019

Journal of Vascular and Interventional Radiology

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“…A caveat for doxorubicin loading was brought to light during this study. Doxorubicin molecules have a tendency to to precipitate in aqueous media, by forming dimers or trimers (de Baere et al 2016). This phenomenon was observed in all microcarrier suspensions that had a minute amount of doxorubicin precipitation adhered to the surface of the Eppendorf tubes.…”

Section: Doxorubicin Release Studymentioning

confidence: 77%

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

Azhar¹

2019

Preprint

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Poly(ethylene glycol) diacrylate (PEGDA)-based cryogel microcarriers incorporated with variable proportion of 3-Sulpho-propyl acrylate (SPA) were synthesized to deliver the broad-spectrum anticancer drug, doxorubicin, in a controlled and sustained method across the blood-brain barrier (BBB) for treatment of glioblastoma multiforme (GBM). Combination of these two polymeric materials was intended to allow the delivery of doxorubicin molecules through the brain parenchyma without prompting multidrug resistance mechanism by the BBB. Due to it its binding affinity to protonated doxorubicin molecules, molar percentage of incorporated SPA into the cryogel microcarriers was hypothesized to be proportional to the level of doxorubicin uptake. To enable droplet formation, fluorinated oil with perfluoropolyether surfactant served as the continuous phase. The prepolymer droplets were fabricated using a T-junction microfluidic device and were crosslinked via photopolymerization. Light microscopy was used for characterization of the microcarriers before and after cryogelation, with regards to size and shape. Doxorubicin loading and release studies were performed to evaluate drug elution rates for each type of microcarrier suspension. Loading of cryogel microcarriers was done at room temperature for a period of 7 days whereas the release study was carried out at 37°C in an incubator for 28 days. Significant differences (p < 0.0001) in uptake and release of doxorubicin, compared to the control, were seen in all SPA incorporated cryogels while those cryogels without any proportion of SPA incorporation had no significant difference ( p > 0.05). Cryogel suspensions with a SPA to PEGDA molar percentage of 60% or less were coherent with the proposed hypothesis, however, microcarriers that had a higher proportion of SPA did not seem to follow this trend. In conclusion, doxorubicin loading and release in cryogel microcarriers is not entirely dependent on its binding affinity with available SPA functional groups, but also on other physiological and mechanical parameters as well.

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Review of the Development of Methods for Characterization of Microspheres for Use in Embolotherapy: Translating Bench to Cathlab

Caine

Carugo

Zhang

et al. 2017

Adv Healthcare Materials

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Microspheres in Advanced Healthcare ApplicationsMicrospheres are small spherical particles with a diameter in the range 1-1000 µm, typically free-flowing in nature that can be made from either synthetic or natural materials (or a combination thereof). They have found widespread use in healthcare applications because numerous methods exist to manufacture Therapeutic embolotherapy is the deliberate occlusion of a blood vessel within the body, which can be for the prevention of internal bleeding, stemming of flow through an arteriovenous malformation, or occlusion of blood vessels feeding a tumor. This is achieved using a wide selection of embolic devices such as balloons, coils, gels, glues, and particles. Particulate embolization is often favored for blocking smaller vessels, particularly within hypervascularized tumors, as they are available in calibrated sizes and can be delivered distally via microcatheters for precise occlusion with associated locoregional drug delivery. Embolic performance has been traditionally evaluated using animal models, but with increasing interest in the 3R's (replacement, reduction, refinement), manufacturers, regulators, and clinicians have shown interest in the development of more sophisticated in vitro methods for evaluation and prediction of in vivo performance. Herein the current progress in developing bespoke techniques incorporating physical handling, fluid dynamics, occlusive behavior, and sustained drug elution kinetics within vascular systems is reviewed. While it is necessary to continue to validate the safety of such devices in vivo, great strides have been made in the development of bench tests that better predict the behavior of these products aligned with the principles of the 3R's.

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An In Vitro Evaluation of Four Types of Drug-Eluting Microspheres Loaded with Doxorubicin

Abstract: Although drug-eluting embolic agents universally loaded doxorubicin within 1 hour, the elution amounts, rates of release, diameter shrinkage, and times in suspension varied by product.

Cited by 76 publications

References 11 publications

An In Vitro Evaluation of Four Types of Drug-Eluting Embolics Loaded with Idarubicin

An In Vitro Evaluation of Four Types of Drug-Eluting Embolics Loaded with Idarubicin

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

Review of the Development of Methods for Characterization of Microspheres for Use in Embolotherapy: Translating Bench to Cathlab

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