Lipiodol-based emulsions used for transarterial chemoembolization and drug delivery: Effects of composition on stability and product quality

Ahnfelt, Emelie; Degerstedt, Oliver; Lilienberg, Elsa; Sjögren, Erik; Hansson, Per; Lennernäs, Hans

doi:10.1016/j.jddst.2019.101143

Cited by 15 publications

(14 citation statements)

References 55 publications

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“…Furthermore, adjustment to the aqueous-to-lipid phase ratio by increasing the Lipiodol ® part (1:2–1:4) enhances the emulsion stability and reduces the drug release rate from the formulation both in vitro and in vivo [ 92 , 95 ]. A recent study reported that the emulsion stability and in vitro release profiles of doxorubicin are both affected by the composition of the aqueous phase and the aqueous-to-lipid phase ratio [ 96 ]. In addition, the relatively low distribution and solubility of doxorubicin to the lipid phase suggest a need for improvements of this DDS.…”

Section: Current Drug Performancementioning

confidence: 99%

Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma

Barbier

Heindryckx

Lennernäs

2021

IJMS

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Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.

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Section: Current Drug Performancementioning

confidence: 99%

Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma

Barbier

Heindryckx

Lennernäs

2021

IJMS

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“…In general, Lipiodol forms an emulsion with a water‐based solution as an oil‐based X‐ray contrast and is injected into the blood vessel. [ 61,62 ] Using the iodized oil property, the Lipiodol‐loaded microrobot can be observed in real‐time through X‐ray imaging during targeting and retrieval because of the unique hydrophobic properties of Lipiodol (Figure 4i). In order to verify the visibility of the microrobot under real‐time X‐Ray for in vivo, a thick three‐layer pork meat was placed on top of the 3D printed channel.…”

Section: Resultsmentioning

confidence: 99%

A Magnetically Guided Self‐Rolled Microrobot for Targeted Drug Delivery, Real‐Time X‐Ray Imaging, and Microrobot Retrieval

Nguyen

Jin

et al. 2021

Adv Healthcare Materials

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Targeted drug delivery using a microrobot is a promising technique capable of overcoming the limitations of conventional chemotherapy that relies on body circulation. However, most studies of microrobots used for drug delivery have only demonstrated simple mobility rather than precise targeting methods and prove the possibility of biodegradation of implanted microrobots after drug delivery. In this study, magnetically guided self‐rolled microrobot that enables autonomous navigation‐based targeted drug delivery, real‐time X‐ray imaging, and microrobot retrieval is proposed. The microrobot, composed of a self‐rolled body that is printed using focused light and a surface with magnetic nanoparticles attached, demonstrates the loading of doxorubicin and an X‐ray contrast agent for cancer therapy and X‐ray imaging. The microrobot is precisely mobilized to the lesion site through automated targeting using magnetic field control of an electromagnetic actuation system under real‐time X‐ray imaging. The photothermal effect using near‐infrared light reveals rapid drug release of the microrobot located at the lesion site. After drug delivery, the microrobot is recovered without potential toxicity by implantation or degradation using a magnetic‐field‐switchable coiled catheter. This microrobotic approach using automated control method of the therapeutic agents‐loaded microrobot has potential use in precise localized drug delivery systems.

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“…Furthermore, once the emulsion is ready to be injected, it is recommended to check for its stability and proper mixing direction. An easily available and reliable way to check direction of an emulsion is the ''drop test'' [60]. The test consists in pushing a droplet out of the syringe within saline or any aqueous liquid.…”

Section: Treatment Deliverymentioning

confidence: 99%

Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE)

Baère

Ronot

Chung

et al. 2022

Cardiovasc Intervent Radiol

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Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) “selectively targetable” and “accessible to supraselective catheterization.” The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5–2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the “drop test.” Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care.

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Lipiodol-based emulsions used for transarterial chemoembolization and drug delivery: Effects of composition on stability and product quality

Cited by 15 publications

References 55 publications

Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma

Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma

A Magnetically Guided Self‐Rolled Microrobot for Targeted Drug Delivery, Real‐Time X‐Ray Imaging, and Microrobot Retrieval

Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE)

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