Systematic development and optimization of spray-dried Quercetin-HP-β-cyclodextrin microparticles for DPI-based therapy of lung cancer

Despite the strong anticancer activity, Quercetin (QC) has low aqueous solubility, resulting in poor bioavailability which restricts its pharmacological activity. To improve the physicochemical-properties and achieve therapeutic potential of QC, solubility enhancement is necessary. We have synthesized QC-HP-β-CD complex and then this complex was spray dried on a semi-industrial scale to form the microparticles (QMP) to achieve the desired aerodynamic characteristic to deliver it in the alveolar region of the lungs. The synthesis of microparticles was systematically optimized by the design of experiment approach to achieve higher product yield. Various critical process parameters were identified, and on this basis, a central composite design was implemented to improve the formulation. The QMP was further characterized for its physicochemical and aerodynamic characteristics and in vitro anticancer activity. QMP has shown 4.72 ± 1.68 µm mean particle size and deflated spherical morphology. The aerodynamic characterization of QMP indicates that particles having low density with more than 80% of particles have an aerodynamic diameter of 1–5 µm. Further, QMP has shown enhanced anti-proliferative efficacy towards A549-adenocarcinomic-alveolar epithelial cell lines. Thus, our results suggest that the synthesized QMP has optimum particle size, aerodynamic characteristics, and potential anticancer activity which make it a suitable dry powder inhaler formulation for the treatment of lung cancer .