Nanovector approach for co-delivery of Alectinib and hesperidin via inhalational for lung cancer treatment: development, characterization, and preclinical studies

The current study aims to fabricate Nanostructured Lipid Carriers for the co-delivery of Alectinib and Hesperidin (ALB-HSD NLC) for non-small cell lung Cancer (NSCLC) via an inhalational route. The ALB-HSD NLC was fabricated using Melt emulsification followed by the sonication method and optimized using a central composite design. The optimized formulation was evaluated for various in vitro and in vivo studies. The optimized ALB-HSD NLC had satisfactory results for particle size, Zeta Potential, PDI, and entrapment efficiency. The drug release was more than 2.5-fold higher compared to drugs suspension over 72 hr. A549 human lung cell line study shows IC50 for ALB and HSD, were 2.289 µg/mL and 73.52 µg/mL, and the dose-dependent toxicity was 0.0209 μg/mL and 0.5213 μg/mL for ALB-HSD NLC formulation and ALB HSD Suspension, respectively, after 72 hr. The Pharmacokinetic study has demonstrated improved AUC0-t (1.38, 1.57-fold) of ALB and HSD from NLC compared to drug suspension. In vivo studies give significant results on the syngeneic model. The prepared ALB-HSD NLC could be promising drug carriers, and they succeeded in delivering small and efficient doses of ALB and HSD to treat NSCLC.