Sustained Zero-Order Release of Intact Ultra-Stable Drug-Loaded Liposomes from an Implantable Nanochannel Delivery System
| Autor: | Alessandro Grattoni, Daniel Fine, Shyam S. Bansal, Maria Grazia Sarpietro, Silvia Ferrati, Erika Zabre, Massimo Fresta, Mauro Ferrari, Christian Celia, Barbara Ruozi, Donatella Paolino, Sharath Hosali, Anne L. van de Ven |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
liposomes
Drug Materials science media_common.quotation_subject Biomedical Engineering Pharmaceutical Science chemotherapy Article Biomaterials Mice Drug Delivery Systems Animals Nanotechnology lapatinib media_common Zero order Liposome Vesicle Intravasation passive targeting Metronomic Chemotherapy Liposomes Circulation time Delivery system Biomedical engineering |
| Popis: | Metronomic chemotherapy supports the idea that long-term, sustained, constant administration of chemotherapeutics, currently not achievable, could be effective against numerous cancers. Particularly appealing are liposomal formulations, used to solubilize hydrophobic therapeutics and minimize side effects, while extending drug circulation time and enabling passive targeting. As liposome alone cannot survive in circulation beyond 48 hrs, sustaining their constant plasma level for many days is a challenge. To address this, we developed, as a proof of concept, an implantable nanochannel delivery system and ultra-stable PEGylated lapatinib loaded-liposomes, and we demonstrate the release of intact vesicles for over 18 days. Further, we investigate intravasation kinetics of subcutaneously delivered liposomes and verify their biological activity post nanochannel release on BT474 breast cancer cells. The key innovation of this work is the combination of two nanotechnologies to exploit the synergistic effect of liposomes, demonstrated as passive-targeting vectors and nanofluidics to maintain therapeutic constant plasma levels. In principle, this approach could maximize efficacy of metronomic treatments. |
| Databáze: | OpenAIRE |
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