Comparative Study of Chemoembolization Loadable Beads: In vitro Drug Release and Physical Properties of DC Bead and Hepasphere Loaded with Doxorubicin and Irinotecan

Jordan, Olivier; Denys, Alban; Baère, Thierry De; Boulens, Nathalie; Doelker, Éric

doi:10.1016/j.jvir.2010.02.042

Cited by 137 publications

(109 citation statements)

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“…Like sunitinib, two other drugs of clinical interest, doxorubicin and irinotecan, can be efficiently loaded into beads, but these drugs display distinct features in terms of elution extent and kinetics (32). In contrast to the complete or almost complete irinotecan and sunitinib elution (100% and 82%, respectively), doxorubicin was partially retained in the beads under saline flow (28% of drug eluted), which could be attributed to stronger ionic interactions with sulfonates or to doxorubicin in situ gelation (33).…”

Section: Preclinical In Vivo Studies With Healthy New Zealand White Rmentioning

confidence: 99%

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

Fuchs

Bize

Dormond

et al. 2014

Journal of Vascular and Interventional Radiology

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Purpose: The combination of embolic beads with a multi-targeted tyrosine kinase inhibitor that inhibits tumor vessel growth is suggested as an alternative and improvement to the current standard doxorubicin-eluting beads for use in transarterial chemoembolization. This study demonstrates the in vitro loading and release kinetics of sunitinib using commercially available embolization microspheres, and evaluates the in vitro biological efficacy on cell cultures and the resulting in vivo pharmacokinetic profiles in an animal model. Materials and Methods:DC Bead microspheres, 70-150 µm and 100-300 µm (Biocompatibles Ltd., Farnham, United Kingdom), were loaded by immersion in sunitinib solution. Drug release was measured in saline in a USP-approved flow-through apparatus and quantified by spectrophotometry. Activity after release was confirmed in cell culture. For pharmacokinetics and in vivo toxicity evaluation, New-Zealand white rabbits received sunitinib either by intra-arterial injection of 100-300 µm sized beads or per os. Drug concentrations in the plasma and liver tissue were assessed by liquid chromatography-tandem mass spectrometry.Results: Sunitinib loading on beads was close to complete and homogeneous. A total release of 80% in saline was measured, with similar fast release profiles for both sphere sizes. After embolization, drug plasma levels remained below the therapeutic threshold (< 50 ng/ml), but high concentrations at 6 h (14.9 µg/g) and 24 h (3.4 µg/g) were found in the liver tissue.Conclusions: DC Bead microspheres of two sizes were efficiently loaded with sunitinib and displayed a fast and almost complete release in saline. High liver drug concentrations and low systemic levels indicated the potential of sunitinib-eluting beads for use in embolization.

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Section: Preclinical In Vivo Studies With Healthy New Zealand White Rmentioning

confidence: 99%

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

Fuchs

Bize

Dormond

et al. 2014

Journal of Vascular and Interventional Radiology

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“…Thus, this practicable set-up was used for preliminary experiments. Microspheres in saline medium in the orbital shaker showed a relatively sustained 180 (t 50% = 4.5 h) and incomplete drug release (84%) for sunitinib (Figure 2), as for doxorubicin (Jordan et al, 2010). This was attributed to the low shear stress in the dissolution flask.…”

Section: Drug Release In An Orbital Shakermentioning

confidence: 96%

“…The drug-ion exchange 200 as a mechanism of loading and release has been demonstrated for other clinically used drugs like irinotecan and doxorubicin (Biondi et al, 2013;Gonzalez et al, 2008;Jordan et al, 2010).…”

Section: Drug Release In Flow-through Implant Cellsmentioning

confidence: 99%

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Sunitinib-eluting beads for chemoembolization: Methods for in vitro evaluation of drug release

Fuchs

Bize

Denys

et al. 2015

International Journal of Pharmaceutics

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Drug-eluting microspheres are used for embolization of hypervascular tumors and allow for 15 local controlled drug release. Although the drug release from the microspheres relies on fast ion-exchange, so far only slow-releasing in vitro dissolution methods have been correlated to in vivo data. Three in vitro release methods are assessed in this study for their potential to predict slow in vivo release of sunitinib from chemoembolization spheres to the plasma, and fast local in vivo release obtained in an earlier study in rabbits. 20Release in an orbital shaker was slow (t 50% = 4.5 h, 84% release) compared to fast release in USP 4 flow-through implant cells (t 50% = 1 h, 100% release). Release of sunitinib from microspheres in saline in dialysis inserts was prolonged and incomplete (t 50% = 9 d, 68% release) due to low drug diffusion through the dialysis membrane. The slow-release profile fitted best to low sunitinib plasma AUC following injection of sunitinib-eluting spheres. Although limited by lack of 25 standardization, release in the orbital shaker fitted best to local in vivo sunitinib concentrations.Drug release in USP flow-through implant cells was too fast to correlate with local concentrations, although this method is preferred to discriminate between different sphere types. 3 Graphical Abstract KeywordsIn vitro drug release, sunitinib, drug-eluting beads, USP dissolution apparatus 4, 35 chemoembolization, in vitro-in vivo correlation

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“…The DC Beads are PVA-based microspheres and range from 75 to 900 mm in size, while the HepaSphere microspheres are superabsorbent polymer based and range from 120 to 800 mm in size. Both systems can be efficiently loaded with doxorubicin (and irinotecan), 44 and preclinical studies have shown safe pharmacokinetic profiles with sustained drug release and antitumour efficacy. [45][46][47] In clinical practice, DEB-TACE has the same indications and contraindications as cTACE.…”

Section: Drug-eluting Beads Transarterial Chemoembolizationmentioning

confidence: 99%

Systematic review of catheter-based intra-arterial therapies in hepatocellular carcinoma: state of the art and future directions

Durán¹,

Chapiro²,

Schernthaner³

et al. 2015

BJR

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Intra-arterial therapies (IATs) play a pivotal role in the management of patients with primary and secondary liver malignancies. The unique advantages of these treatments are their ability to selectively deliver a high dose of anticancer treatment while preserving healthy liver tissue. The proven efficacy of these catheter-based locoregional therapies in a highly systemic chemoresistant cancer such as hepatocellular carcinoma (HCC), along with the minimally invasive nature of these treatments, quickly yielded wide acceptance in the medical community and revolutionized the field of Interventional Oncology. In this article, we describe the clinical rationale and background of catheter-based IATs. We provide an overview of clinical achievements of these treatments alone and in combination with sorafenib in patients with HCC.

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Comparative Study of Chemoembolization Loadable Beads: In vitro Drug Release and Physical Properties of DC Bead and Hepasphere Loaded with Doxorubicin and Irinotecan

Cited by 137 publications

References 12 publications

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

Sunitinib-eluting beads for chemoembolization: Methods for in vitro evaluation of drug release

Systematic review of catheter-based intra-arterial therapies in hepatocellular carcinoma: state of the art and future directions

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