Locoregional drug delivery using image-guided intra-arterial drug eluting bead therapy

Abstract

Lipiodol-based transarterial chemoembolization (TACE) has been performed for over 3 decades for the treatment of solid tumors and describes the infusion of chemotherapeutic agents followed by embolization with particles. TACE is an effective treatment for inoperable hepatic tumors, especially hypervascular tumors such as hepatocellular carcinoma. Recently, drug eluting beads (DEBs), in which a uniform embolic material is loaded with a drug and delivered in a single image-guided step, have been developed to reduce the variability in a TACE procedure. DEB-TACE results in localization of drug to targeted tumors while minimizing systemic exposure to chemotherapeutics. Once localized in the tissue, drug is eluted from the DEB in a controlled manner and penetrates hundreds of microns of tissue from the DEB surface. Necrosis is evident surrounding a DEB in tissue days to months after therapy; however, the contribution of drug and ischemia is currently unknown. Future advances in DEB technology may include image-ability, DEB size tailored to tumor anatomy and drug combinations.

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

“…Transarterial chemoembolisation (TACE) has been used for over 30 years and is performed by local arterial infusion of the chemotherapeutic agent and subsequent injection of embolic particles [5]. Thus, it synergistically combines tumour starvation caused by embolisation [6,7], with the cytotoxic effect of drugs whilst minimising the systemic toxicity [8,9].…”

“…Thus, it synergistically combines tumour starvation caused by embolisation [6,7], with the cytotoxic effect of drugs whilst minimising the systemic toxicity [8,9]. TACE has been demonstrated to be particularly effective for treating hypervascularised tumours and especially hepatic malignant lesions, which derive their main blood supply from arterial vessels [5]. Whilst the advantages of TACE with respect to systemic chemotherapy have been widely demonstrated [10][11][12], there still persists a lack of method standardisation among clinicians in terms of properties of the embolic device and administration techniques to be employed for achieving a desired therapeutic effect [5,13].…”

“…TACE has been demonstrated to be particularly effective for treating hypervascularised tumours and especially hepatic malignant lesions, which derive their main blood supply from arterial vessels [5]. Whilst the advantages of TACE with respect to systemic chemotherapy have been widely demonstrated [10][11][12], there still persists a lack of method standardisation among clinicians in terms of properties of the embolic device and administration techniques to be employed for achieving a desired therapeutic effect [5,13]. In order to address these issues, drug-eluting beads (DEBs) in the form of calibrated deformable microspheres have been introduced as embolic devices [14].…”

Oscillation dynamics of embolic microspheres in flows with red blood cell suspensions

“…[1][2][3][4][5] Embolization is defined as a process by which the blood vessels close to tumor site can be blocked with micron sized particles in order to cut off the local nutrient supply or to deliver therapeutic chemicals (chemoembolization) and radioactive materials (radioembolization) for destruction of cancer cells in a site specific manner. 2,[6][7][8] With the advent of narrow catheters with diameters close to 1 mm, embolization therapy has been perceived to be a major protocol towards minimal incision strategy. 9,10 To facilitate the embolization process, microparticles such as spherical microbeads or microspheres are employed.…”

“…[13][14][15][16][17] Axial and lateral translations of suspended particles in inertial yet Newtonian fluid flow are amenable to matchedasymptotic analysis if particle diameters are infinitesimally small compared to the channel diameter (d c ), i.e., relative particle diameter a ¼ d p =d c ( 1, essentially implicating the considerations of particles as point masses. However, for microspheres (d p ¼ 100-300 lm) translating within small arteries (d c $ 1 mm), 1,3,6,10 confinement effects dictated by finite values of a may turn out to be critical in determining the particle dynamics. Relevantly, for Newtonian fluid flows through narrow confinements, the cross-stream particle migration at inertial Reynolds number (Re) regimes has been analyzed and engineered towards microfluidic particle separator design and optimization.…”