Nanostructured polyelectrolyte multilayer drug delivery systems for bone metastasis prevention.
Polyelectrolyte multilayers (PEM) are well established nanoarchitectures with numerous potential applications, in particular as biomaterial coatings. They may exhibit specific biological properties in terms of controlled cell activation or local drug delivery. Here, in a new approach for bone metastasis prevention, we employed poly-l-lysine covalently grafted with beta-cyclodextrin as a polycationic vector (PLL-CD) for the antitumor bisphosphonate drug risedronate (RIS). Molar ratio for maximum loading of the PLL-CD vector with RIS was determined by Raman microspectroscopy. The efficacy of RIS at inhibiting cancer cell invasion in vitro was strongly enhanced upon complexation, whatever PLL-CD:RIS complexes were in solution or embedded into PEM nanoarchitectures. Complexes in solution also clearly prevented cancer-induced bone metastasis in animals. Incorporation of the complexes into PEM nanoarchitectures covering bone implants appears of interest for in situ prevention of bone metastasis after ablation.
Daubiné
Florence
F
INSERM U664 and Université Claude Bernard Lyon 1, Faculté de Médecine Laënnec, 69372 Lyon, France.
Cortial
Delphine
D
Ladam
Guy
G
Atmani
Hassan
H
Haïkel
Youssef
Y
Voegel
Jean-Claude
JC
Clézardin
Philippe
P
Benkirane-Jessel
Nadia
N
D000818:Animals; D000969:Antinematodal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000517:prevention & control*; D016503:Drug Delivery Systems; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry* / Q000592:standards* / Q000627:therapeutic use*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D000068296:Risedronic Acid; D013059:Spectrum Analysis, Raman; D047392:beta-Cyclodextrins / Q000737:chemistry
D000969:Antinematodal Agents; D047392:beta-Cyclodextrins; C031215:betadex; D000068296:Risedronic Acid; D012968:Etidronic Acid