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.
Injectable polymer microparticles with the ability to carry and release pharmacologically active agents are attracting more and more interest. This study is focused on the chemical synthesis, characterization, and preliminary exploration of the utility of a new type of injectable drug-releasing polymer microparticle. The particles feature a new combination of structural and physico-chemical properties: (i) their geometry deviates from the spherical in the sense that the particles have a cavity; (ii) the particles are porous and can therefore be loaded with crystalline drug formulations; drug crystals can reside at both the particle’s surfaces and inside cavities; (iii) the particles are relatively dense since the polymer network contains covalently bound iodine (approximately 10% by mass); this renders the drug-loaded particles traceable (localizable) by X-ray fluoroscopy. This study presents several examples. First, the particles were loaded with crystalline voriconazole, which is a potent antifungal drug used in ophthalmology to treat fungal keratitis (infection/inflammation of the cornea caused by penetrating fungus). Drug loading as high as 10% by mass (=mass of immobilized drug/(mass of the microparticle + mass of immobilized drug) × 100%) could be achieved. Slow local release of voriconazole from these particles was observed in vitro. These findings hold promise regarding new approaches to treat fungal keratitis. Moreover, this study can help to expand the scope of the transarterial chemoembolization (TACE) technique since it enables the use of higher drug loadings (thus enabling higher local drug concentration or extended therapy duration), as well as application of hydrophobic drugs that cannot be used in combination with existing TACE embolic particles.
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