Development of paclitaxel nanocrystal-based dry powder formulations for targeted therapy of lung tumours by inhalation  

Rémi Rosière¹, Selma Chraibi¹, Sara Albasry¹, Marjorie Vermeersch², Karim Amighi¹ & Nathalie Wauthoz¹

¹Laboratory of Pharmaceutics and Biopharmaceutics, Faculty of Pharmacy, Université libre de Bruxelles (ULB), Boulevard du Triomphe, B-1050 Brussels, Belgium, [email protected]

²Center for Microscopy and Molecular Imaging (CMMI), 8 Rue Adrienne Bolland, B-6041 Gosselies, Belgium 

Summary

Introduction. Nanomedicine-based dry powders for inhalation are promising in aerosolized anticancer chemotherapy in order to penetrate lung tumours and cancer cells and limit lung and systemic toxicities. In previous works, we developed nanocarrier-based formulations with lung tumour and cancer cell penetration and good aerodynamic properties but with a low paclitaxel (PTX) loading. Delivering effective high PTX doses to patients was therefore not possible by means of these formulations. In this work, we aimed to (i) develop PTX nanocrystals, (ii) coat them with a folate-grafted copolymer and finally (iii) embed them in a solid matrix to form dry powders for inhalation with a high PTX content. Methods. Paclitaxel nanocrystals coated with the F-PEG-HTCC copolymer were prepared using high speed and high pressure homogenization techniques. They were characterized in terms of size, charge, morphology and in vitro PTX release profile. Dry powders were prepared by spray-drying F-PEG-HTCC-coated PTX nanocrystals in the presence of mannitol. The PTX loading, morphology and aerodynamic properties were determined. Results and discussion. F-PEG-HTCC-coated PTX nanocrystals were prepared with Z-average mean diameter of 332 nm and a zeta potential of +13 mV. The best dry powder formulation had a good ability to re-disperse the initial coated nanocrystals in water and a PTX loading of 3.4%. It presented good aerodynamic properties, with an FPD of 180 µg, corresponding to an FPF_nom of 45%. Conclusion. The best dry powder formulation had acceptable physicochemical and aerodynamic properties for going further in development, i.e. efficacy and safety studies in animal models.