Formulation of Folate Receptor-Targeted Silibinin-Loaded Inhalable Chitosan Nanoparticles by the QbD Approach for Lung Cancer Targeted Delivery.

: Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. The main objective of this research was to develop folate receptor-targeted silibinin (SB)-loaded inhalable polymeric nanoparticles (FA-CS-SB-NPs) for the treatment of lung cancer. : The qbD approach was implemented to prepare SB-loaded nanoparticles. Folic acid was conjugated by electrostatic conjugation in an optimized batch. The therapeutic potentials of formulations were determined using a lung cancer cell-bearing rat model. : Optimized formulation exhibited a spherical surface with a mean particle size of 275 ± 1.20 nm, a PDI of 0.234 ± 0.07, a ζ-potential of 32.50 ± 0.21, an entrapment efficiency of 75.52 ± 0.87%, and a CDR of 63.25 ± 1.21% at 48 h. Aerodynamic behaviors such as the mass median aerodynamic diameter (MMAD) and geometric size distribution (GSD) were found to be 2.75 ± 1.02 and 3.15 ± 0.88 μm, respectively. After 24 h of incubation with FA-CS-SB-NPs, the IC50 value was found to be 24.5 g/mL. FA-SB-CS-NPs maintained a significantly higher deposition of SB in lung tissues. : Thus, the noninvasive nature and target specificity of FA-CS-SB-NPs pave the way for pulmonary delivery for treating lung cancer.