Embolic microspheres for transarterial chemo-embolization (TACE) featuring inherent radiopacity and carrying crystalline drugs at their surface, in dimples or inside major cavities

Abstract

Abstract Transarterial chemoembolization (TACE) using drug-eluting embolic (DEE) microparticles is a minimally invasive treatment technique that finds more and more applications in oncology, particularly in the treatment of patients with hepatocellular carcinoma. The last decade has seen marked developments in TACE, mainly due to innovations regarding the embolic microparticles. We studied a new versatile approach for charging TACE embolic particles (3D-crosslinkled polymer microspheres) with crystalline (cytostatic) drugs. The crystals are physically attached to the microporous particles. This approach provides a promising alternative for the ion-exchange regime that underlies the mechanism of action of all TACE/DEE products which are currently available commercially. Moreover, chemical synthesis is reported of new nearly spherical polymeric microparticles which either have a cavity or one or more dimples in their surface. These particles are remarkable since (i), the cavity or dimples can accommodate relatively large drug crystals in a stable manner, and (ii), their size is 1–2 orders of magnitude larger than similar shapes known in the literature. The large diameter (ranging from 200 to 600 µm roughly) renders the new particles suitable for TACE/DEE. It is argued and underpinned that the use of crystalline drug formulations according to this methodology can open new possibilities for TACE in the treatment of different solid cancers, particularly since (i), larger drug payloads can be achieved, and (ii), new options emerge to use lipophilic crystalline drugs which have been incompatible with TACE hitherto. Since many potent cytostatic medicines fall into this category, the new technique can likely become scope-widening for the TACE technique.