RESUMEN
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.
Asunto(s)
Composición de Medicamentos , Embolización Terapéutica , Microesferas , Polímeros/química , HumanosRESUMEN
The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.
Asunto(s)
Virus del Dengue , Dengue/diagnóstico , Microfluídica/métodos , Microesferas , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Metacrilatos/química , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/instrumentación , Tamaño de la Partícula , Ácidos Polimetacrílicos/química , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Biodegradable poly(D,L-lactic acid) drug-eluting microspheres containing anti-tumor drugs, cisplatin, and sorafenib tosylate have been prepared by the emulsion solvent evaporation method with diameter between 200 and 400 µm. Scanning electron microscopy showed that cisplatin microspheres had smooth surfaces, while sorafenib tosylate microspheres and cisplatin + sorafenib tosylate microspheres were porous at the surface and the pits of the latter were larger than those of the former. Notably, cisplatin + sorafenib tosylate microspheres had a fast drug release rate compared with microspheres containing one drug alone. In vitro cytotoxicity experiments and classical matrigel endothelial tube assay certificated the maintaining bioactivity of cisplatin and sorafenib tosylate released from the microspheres, respectively. This work provides a useful approach for the fabrication of drug-eluting beads used in transarterial chemoembolization.