Inhalable spray dried lipidnanoparticles for the co-delivery of paclitaxel and doxorubicin in lung cancer

The present study aimed to develop and evaluate inhalable nanocarriers using different surfactants for enhancing the antitumor efficacy of chemotherapeutics. Surfactants (Cremophor EL, Tween 80 and Tween 20) loaded nano-lipid carriers (NLCs) containing Paclitaxel (PTX) and Doxorubicin (DOX) were prepared through solvent evaporation followed by spray drying technique. The prepared inhalable nanoaggregates were evaluated for various pharmaceutical and aerodynamic properties. Animal model was used to determine in-vivo drug distribution, and safety profile of optimized formulations. Particle size distribution analysis indicated that Cremophor EL based nanocarriers have smallest particle size distribution (394.1 ± 5.6 nm) compared to Tween 80 and Tween 20 characterized by size values, 575.6 ± 3.3 nm and 460.7 ± 2.6 nm, respectively. DSCand XRD analysis show no characteristic change in solid state properties of drugs in optimized formulation. Organ distribution studies demonstrated Cremophor EL DPIs show higher drug distribution in the lungs compared to other experimental formulations and plain drugs. Further animals treated with experimental DPIs show no sign of tissue damage with usual feeding and drinking behaviour after 24 h of treatment. In this study, spray-dried nanoaggregates composed of Cremophor EL encapsulating PTX and DOX offer a possible strategy to reverse the growing concern of drug resistance for improved therapeutic adherence.