RESUMO
AIM: To compare the pharmacokinetics and efficacy of doxorubicin containing plant virus nanoparticles (PVNs) with PEGylated liposomal doxorubicin (PLD) and small molecule doxorubicin in two mouse models of cancer. MATERIALS & METHODS: Studies were performed in A375 melanoma and intraperitoneal SKOV3ip1 ovarian cancer xenografts. The PVNs were administered in lower and more frequent doses in the ovarian model. RESULTS: The PVNs were more efficacious than PLD and small molecule doxorubicin in the ovarian cancer model, but not in the melanoma cancer model. The pharmacokinetics profiles of the PVNs showed fast plasma clearance, but more efficient tumor delivery as compared with other carrier-mediated agents. CONCLUSION: PVNs administered at lower repeated doses provide both pharmacologic and efficacy advantages compared with PLD.
Assuntos
Antineoplásicos/farmacocinética , Doxorrubicina/análogos & derivados , Vírus do Mosaico/química , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/toxicidade , Química Farmacêutica/métodos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidade , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Cinética , Camundongos , Camundongos SCID , Microscopia Eletrônica de Transmissão/métodos , Tamanho da Partícula , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/toxicidade , Propriedades de Superfície , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
We present a novel technology for microfluidic elastometry and demonstrate its ability to measure stiffness of blood clots as they form. A disposable micro-capillary strip draws small volumes (20 µL) of whole blood into a chamber containing a surface-mounted micropost array. The posts are magnetically actuated, thereby applying a shear stress to the blood clot. The posts' response to magnetic field changes as the blood clot forms; this response is measured by optical transmission. We show that a quasi-static model correctly predicts the torque applied to the microposts. We experimentally validate the ability of the system to measure clot stiffness by correlating our system with a commercial thromboelastograph. We conclude that actuated surface-attached post (ASAP) technology addresses a clinical need for point-of-care and small-volume elastic haemostatic assays.