title: Sustained zero-order release of intact ultra-stable drug-loaded liposomes from an implantable nanochannel delivery system.
abstract: 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 h, sustaining their constant plasma level for many days is a challenge. To address this, we develop, 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 d. 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.
authors.affiliation: Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA; Department of Health Sciences, University "Magna Graecia" of Catanzaro, V.le "S. Venuta" Germaneto-Catanzaro 88100, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Celia
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferrati
authors.forename: Shyam
authors.initials: S
authors.lastname: Bansal
authors.forename: Anne L
authors.initials: AL
authors.lastname: van de Ven
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruozi
authors.forename: Erika
authors.initials: E
authors.lastname: Zabre
authors.forename: Sharath
authors.initials: S
authors.lastname: Hosali
authors.forename: Donatella
authors.initials: D
authors.lastname: Paolino
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sarpietro
authors.forename: Daniel
authors.initials: D
authors.lastname: Fine
authors.forename: Massimo
authors.initials: M
authors.lastname: Fresta
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Alessandro
authors.initials: A
authors.lastname: Grattoni
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D036103:Nanotechnology / Q000379:methods*
chemical_list: D008081:Liposomes
keywords: constant release; implantable device; liposomes; nanochannels; subcutaneous delivery