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

Abstract

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.

Polymeric Microspheres Designed to Carry Crystalline Drugs at Their Surface or Inside Cavities and Dimples

“…Recently we reported on non-spherical particles, which consisted of the same biomaterial and contained a relatively large cavity [ 28 ]. While we could show that the cavity of such particles could be partially filled with the crystalline drug (voriconazole was used as an example), we realized that round beads are preferred for TACE [ 29 , 30 , 31 ]. Hence, our specific aim was to study possible ways to obtain spherical DEE microparticles loaded with the crystalline drug, find ways to maximize the drug payload, and study the release of the drug in vitro.…”

“…We set out to study the drug-loaded spherical and near-spherical/cavitated particles with the drug voriconazole. We have a longstanding interest in this drug [ 29 ], and we are working on new technologies for sustained administration of voriconazole to the eye’s tear film, thereby using microsphere technologies. Furthermore, we considered this drug as an adequate model for many cytostatic agents that are used in combination with TACE, in view of its comparably poor solubility in aqueous media and its molecular mass.…”