A new biodegradable and biocompatible poly(ester amide)s (PEAs) polymer based on non-toxic building block which is ?-amino acid histidine, and Isosorbide had been synthesized to be a carrier for inhalation drugs, since this class of polymer gained particular importance in the biomedical field due to the lower toxicity of their degraded products, as well an excellent mechanical and thermal properties. Choosing pulmonary drug delivery of fluticasone propionate which is used to treat chronic obstructive pulmonary disease (COPD) and asthma through dry powder inhalers (DPI)s was due to its rapid pharmacological response with minimal side effects and non-invasive method. Therefore, the aim of this study was to synthesize a new biodegradable and biocompatible PEA polymer and incorporate it with fluticasone propionate as a DPI. Histidine-isosorbide monomer was synthesized and subsequently polymerized using the interfacial polymerization method. Then, FP polymer was synthesized using the same method. The produced monomer and polymer were characterized through solubility test, Fourier transform infrared spectroscopy (FTIR), solution viscosity (?inh), and Nuclear magnetic resonance spectroscopy (NMR). Then a quantitative method for the analysis of fluticasone propionate by High performance liquid chromatography (HPLC) was validated according to the International Council for Harmonization (ICH) guidelines. To study the efficacy of this formula and the lung deposition, it was characterized using Next generation impactor (NGI) for mass median aerodynamic diameter (MMAD), emitted dose (ED), fine particle fraction (FPF), and content uniformity and all these parameters were compared with a market drug with the same pharmaceutical active ingredient (API). The results revealed that the monomer and PEAs structures were confirmed by FTIR, 1H and 13C NMR spectroscopy, the ?inh was 0.32 dL/g for the PEA and decreased for the FP polymer to be 0.24 dL/g. The FP polymer MMAD was 1.615 ?m, while the ED was 89.5%. Regarding the FPF of the ED it was 57%, as for content uniformity it was excellent and within the range. Therefore, the outcome of this research project is that PEAs polymer based on histidine and isosorbide can be a potential carrier for respiratory drug delivery with favorable attributes.