Background: The use of polymer based nanoparticles (NPs), poly(glycerol adipate-co-ω-pentadecalactone) and chitosan for inhalation by spray drying process were evaluated for formulation parameters, mannitol sugar and leucine amino acid as excipient, concentration, and ratio of NPs to excipient.. The aim of this study was to design and formulate [PGA-co-PDL] and naturally occurring cationic chitosan nanoparticles within microparticle carriers (NCMPs) for pulmonary delivery. Methods : PGA-co-PDL, NPs were prepared via an oil in water (o/w) single emulsion solvent evaporation method using DOTAP (%w/v) to produce cationic NPs. Chitosan solution was prepared at concentration of 0.2% in 1% acetic acid buffer (pH:6). 5 formulations (F1-F5) were used to optimise different parameters such as sugar (mannitol) and amino acid (leucine) excipient, concentration and ratio of NPs to excipient, atomized air flow, aspirator capacity, feed rate, inlet/outlet temperature to formulate and achieve particles of desired yield, size and shape with low moisture content to target lung cancer cells. Results: Optimum PGA-co-PDL and chitosan NCMPs resulted in recovered nanoparticle size < 500 nm. Spray drying resulted in NCMPs over 65% yield. Optimum formulation theoretical dynamic diameter dae was 0.63±0.01 and 0.82±0.02 μm and formulations containing higher percentage mannitol showed lower moisture content 2.02±0.03 and 0.57±0.006 for PGA-co-PDL and chitosan NCMPs respectively. The tapped density of PGA-co-PDL and Chitosan NCMPs were relatively similar (0.14±0.01 and 0.35±0.03 g cm-3 ). Conclusion: The results indicated optimum spray drying of NCMPs containing mixture of leucine and mannitol (25:75% w/w) with PGA-co-PDL and chitosan NPs, which can be applied for dry powder inhalation.