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

Abstract

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.

Single-Cell Microgels: Technology, Challenges, and Applications

“…A spherical microgel morphology is ideal for several applications: spherical particles (i) conformally embed suspended cells, thereby providing isotropic 3D biochemical and biophysical stimuli; (ii) result in less clogging compared with irregularly shaped microparticles, which, for example, enables injection of higher microgel concentrations using thinner needles [87]; (iii) cause less intense inflammatory responses upon in vivo implantation [88]; and (iv) intrinsically form predictable and well-controlled interconnected networks upon stacking, which promotes solute diffusion and tissue ingrowth (e.g., vascularization) [85].…”

Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy

“…Therapeutic utility of embolic bodies is further enhanced with the design of DEB, specifically using hydrogel biomaterials. The use of hydrogels in these systems is advantageous over “solid” beads in that hydrogels are soft, nondamaging to the vasculature, and can adapt their shape for deeper penetration into the vascular bed . Commercially available embolic beads (e.g., DC Beads) are based on poly(vinyl alcohol), a polymer which we have previously used for the development of EPT in the context of implantable biomaterials .…”

A versatile UCST-type composite microsphere for image-guided chemoembolization and photothermal therapy against liver cancer

“…6,7 Therefore, the performance of the chemoembolization vectors is the key determinant of TACE outcome. [8][9][10] The major goal of TACE is to achieve complete tumor necrosis, thus providing patients with survival benefits as much as possible. It has been demonstrated that the magnitude of tumor necrosis, in terms of treatment response which is usually assessed by contrast enhanced imaging studies, correlated closely with prognosis.…”

“…DEB release per loaded drugs via ion-exchange mechanism in a slow and sustained release pattern to deliver chemotherapeutic agents toward tumor lesions continuously. [8][9][10] However, being intrinsically drug-resistant in nature, liver cancer is notorious for being refractory to either systemic or transarterial infusion chemotherapy. 4,16 Furthermore, conclusive evidence supporting the superiority of TACE over transarterial embolization (TAE) is still absent, suggesting the poor performance of chemotherapy for liver cancer.…”