New lung-tumour-penetrating nanocarrier designed for aerosolized chemotherapy

Rémi Rosière, Karim Amighi, Nathalie Wauthoz, Matthias Van Woensel; Véronique Mathieu; Thomas Mathivet;

In lung cancer therapy, inhaled nanomedicine could improve systemic nanomedicine-based chemotherapy by delivering high amounts of nanocarriers directly to the lung tumour site. However, penetration of the nanocarriers into a solid tumour remains difficult, whatever the selected route of administration.
The aim of this study was therefore to develop a tumour-selective nanocarrier for inhalation that is able to penetrate lung tumour cells and tissues.
Solid lipid nanoparticles (SLN) coated with a folate-grafted chitosan copolymer were prepared by a nanoprecipitation method with a paclitaxel entrapment efficiency of ~100%. Efficient coating was confirmed by particle size and zeta potential (Z-average mean diameter of 160 nm to 230 nm and zeta potential of -20 mV to +30 mV before and after coating, respectively). The coated SLN were characterized by significantly higher anti-proliferative properties than Taxol®, with half-maximal inhibitory concentrations of 60 and 340 μM, respectively, as observed by means of the colorimetric MTT assay. Interestingly, the nanocarrier was able to enter HeLa and M109-HiFR, two folate receptor (FR)-expressing cell lines, in vitro, and in vivo after administration by inhalation to orthotopic M109-HiFR lung-tumour-grafted mice. The SLN remained coated with the folate-grafted copolymer in lung tissues and tumours after inhalation.
This study therefore demonstrated the potential for a new FR-targeted nanocarrier to reach, penetrate and distribute throughout lung tumour tissues after inhalation.

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