Predicting pharmacokinetic behaviour of drug release from drug-eluting embolization beads using in vitro elution methods

Hagan, Alice; Caine, Marcus; Press, Cara; Macfarlane, Wendy M.; Phillips, Gary; Lloyd, Andrew W.; Czuczman, Peter; Kilpatrick, Hugh; Bascal, Zainab; Tang, Yiqing; García, Pedro López; Lewis, Andrew L.

doi:10.1016/j.ejps.2019.05.021

Cited by 25 publications

(36 citation statements)

References 35 publications

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“…Due to poor water solubility and lenvatinib precipitation, these results indicate an inappropriateness of apoferritin to encapsulate lenvatinib. On the contrary, Van should be protonated during the encapsulation process [35,36]. The positive charge of the majority of Van molecules was confirmed in our laboratory during metabolic experiments [37].…”

Section: Discussionmentioning

confidence: 83%

Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib

Jáklová

Feglarova

Rex

et al. 2021

IJMS

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A tyrosine kinase inhibitor, vandetanib (Van), is an anticancer drug affecting the signaling of VEGFR, EGFR and RET protooncogenes. Van is primarily used for the treatment of advanced or metastatic medullary thyroid cancer; however, its usage is significantly limited by side effects, particularly cardiotoxicity. One approach to minimize them is the encapsulation or binding of Van in- or onto a suitable carrier, allowing targeted delivery to tumor tissue. Herein, we constructed a nanocarrier based on apoferritin associated with Van (ApoVan). Based on the characteristics obtained by analyzing the average size, the surface ζ-potential and the polydispersive index, ApoVan nanoparticles exhibit long-term stability and maintain their morphology. Experiments have shown that ApoVan complex is relatively stable during storage. It was found that Van is gradually released from its ApoVan form into the neutral environment (pH 7.4) as well as into the acidic environment (pH 6.5). The effect of free Van and ApoVan on neuroblastoma and medullary thyroid carcinoma cell lines revealed that both forms were toxic in both used cell lines, and minimal differences between ApoVan and Van were observed. Thus, we assume that Van might not be encapsulated into the cavity of apoferritin, but instead only binds to its surface.

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Section: Discussionmentioning

confidence: 83%

Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib

Jáklová

Feglarova

Rex

et al. 2021

IJMS

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“…During the last 10–15 years, we witnessed the development and clinical introduction of so‐called drug‐eluting beads (DEBs) to be used in TACE 14 . These are embolic polymer microspheres loaded with a chemotherapeutic agent, such as doxorubicin, irinotecan, idarubicin, and sunitinib 15‐26 . A particularly attractive feature of drug‐eluting embolic beads (DEB‐TACE) is that toxic side‐effects of the drug to healthy parts of the body are largely avoided.…”

Section: Introductionmentioning

confidence: 99%

“…Also, post‐procedural imaging of the embolic particles will help to assess the outcome of the procedure. This radiopaque DEB, developed and brought to the market by Biocompatibles plc (Farnham GU9 8QL, United Kingdom), carries the name DC‐Bead LUMI 24 …”

Section: Introductionmentioning

confidence: 99%

“…This radiopaque DEB, developed and brought to the market by Biocompatibles plc (Farnham GU9 8QL, United Kingdom), carries the name DC-Bead LUMI. 24 Our work in this field has followed a reverse order: we first developed X-ray imageable polymeric embolic microspheres, [34][35][36] and we are now engaged in modifying these into X-ray-imageable drugeluting embolic beads. Our initial R&D work on radiopaque embolic microspheres for TACE has been translated into a commercial embolization product that was coined X-Spheres, and that received CE certification in 2012.…”

Section: Introductionmentioning

confidence: 99%

“…14 These are embolic polymer microspheres loaded with a chemotherapeutic agent, such as doxorubicin, irinotecan, idarubicin, and sunitinib. [15][16][17][18][19][20][21][22][23][24][25][26] A particularly attractive feature of drug-eluting embolic beads (DEB-TACE) is that toxic side-effects of the drug to healthy parts of the body are largely avoided. Such side-effects frequently become very problematic when chemotherapeutics are administered systemically (e.g., via intravenous injection).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polymer microparticles with a cavity designed for transarterial chemo‐embolization with crystalline drug formulations

et al. 2020

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Transarterial chemo‐embolization with drug‐eluting embolic beads (DEB‐TACE) is still evolving. Recent developments include the introduction of radiopaque (X‐ray imageable) drug‐eluting particles. Here, we report on conceptually different radiopaque polymeric drug‐eluting embolic particles, which are (i), cross‐linked poly(methacrylates); (ii), radiopaque; (iii), microporous. Furthermore, the particles are not perfectly spherical: they have a large indentation in the sense that they are either a spherical/cup‐shaped or ellipsoid/mouth‐shaped. The micropores and the large indentation can confer useful features upon the particles, since they can be filled with a crystalline lipophilic chemotherapeutic drug. It is important, in this respect that (i), many potent chemotherapeutics are lipophilic and crystalline; (ii), available drug‐eluting beads (DEBs) have the limitation that they can only be used in combination with water‐soluble chemotherapeutic agents. Cup‐ and mouth‐shaped particles were obtained in a Cu(0) catalyzed free‐radical polymerization reaction. The microparticles could be charged with crystalline drug, in such a manner that the crystals reside in both the micropores and the large cavity, and in quantities that would be required for effective local chemotherapy. The antifungal drug voriconazole, lipophilic, and crystalline, was used to demonstrate this. We believe that the ability of the microporous/cavitated DEBs to carry lipophilic chemotherapeutic drugs is especially important. DEB‐TACE is likely to become a cornerstone method of interventional oncology in the years ahead, and the new embolic particles described herein hold the promise of becoming scope widening for the technique.

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A 3D Tumor‐Mimicking In Vitro Drug Release Model of Locoregional Chemoembolization Using Deep Learning‐Based Quantitative Analyses

et al. 2023

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Primary liver cancer, with the predominant form as hepatocellular carcinoma (HCC), remains a worldwide health problem due to its aggressive and lethal nature. Transarterial chemoembolization, the first-line treatment option of unresectable HCC that employs drug-loaded embolic agents to occlude tumor-feeding arteries and concomitantly delivers chemotherapeutic drugs into the tumor, is still under fierce debate in terms of the treatment parameters. The models that can produce in-depth knowledge of the overall intratumoral drug release behavior are lacking. This study engineers a 3D tumor-mimicking drug release model, which successfully overcomes the substantial limitations of conventional in vitro models through utilizing decellularized liver organ as a drug-testing platform that uniquely incorporates three key features, i.e., complex vasculature systems, drug-diffusible electronegative extracellular matrix, and controlled drug depletion. This drug release model combining with deep learning-based computational analyses for the first time permits quantitative evaluation of all important parameters associated with locoregional drug release, including endovascular embolization distribution, intravascular drug retention, and extravascular drug diffusion, and establishes long-term in vitro-in vivo correlations with in-human results up to 80 d. This model offers a versatile platform incorporating both tumor-specific drug diffusion and elimination settings for quantitative evaluation of spatiotemporal drug release kinetics within solid tumors.

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Predicting pharmacokinetic behaviour of drug release from drug-eluting embolization beads using in vitro elution methods

Cited by 25 publications

References 35 publications

Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib

Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib

Polymer microparticles with a cavity designed for transarterial chemo‐embolization with crystalline drug formulations

A 3D Tumor‐Mimicking In Vitro Drug Release Model of Locoregional Chemoembolization Using Deep Learning‐Based Quantitative Analyses

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