Sustained zero-order release of intact ultra-stable drug-loaded liposomes from an implantable nanochannel delivery system

Christian Celia, Silvia Ferrati, Shyam Bansal, Anne L. van de Ven, Barbara Ruozi, Erika Zabre, Sharath Hosali, Donatella Paolino, Maria Grazia Sarpietro, Daniel Fine, Massimo Fresta, Mauro Ferrari, Alessandro Grattoni

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)230-238
Number of pages9
JournalAdvanced Healthcare Materials
Volume3
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Constant release
  • Implantable device
  • Liposomes
  • Nanochannels
  • Subcutaneous delivery

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Pharmaceutical Science

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