Large scale production of therapeutic nanoparticles (NPs) is still challenging. Herein, we report a facile single step electrospray process for the production of a nanocarrier platform made of hybridized chitosan (CS)/ polyvinyl alcohol (PVA) matrix. The method was adapted to achieve the lowest NPs size for carrying and delivering a hydrophobic anti-cancer drug, magnolol (Mag). To improve the inhalation properties of the optimized NPs formulation, the spray drying method was adopted to generate Mag loaded nano embedded-in-microparticles (Mag-NEM). The impact of the characteristics of CS and PVA blended solutions with and without Mag on the developed systems was investigated. The viscosity of the polymers solution played a major role on the size of electrosprayed NPs. NPs could only be obtained at CS:PVA ratio 7:3 and 8:2 for low molecular weight CS and at only 8:2 ratio for the medium molecular weight. Mag-NPs scoring 415.7 nm with a high drug encapsulation efficiency of 95.5% ±2.5 were successfully prepared at 0.1 mL/h flow rate, 15 cm tip to collector distance and 25 kV applied voltage. Optimized Mag-NEM exhibited good aerosolization properties with effective inhalation index of 64.69% and showed a two-fold decrease in IC50 when challenged against lung cancer cells A549.