The pulmonary route for drug delivery offers multiple advantages for local and systematic delivery of active pharmaceutical ingredients (API). Electronic nicotine delivery systems or e-cigarettes are popular devices, which produce an aerosol from a solution containing nicotine, flavorings, and other additives for inhalation by mouthpiece. In 2021, the global sales of vaping devices and e-liquids reached $18.13 billion and is reported as very popular for use particularly among teenagers. The liquid of e-cigarettes called e-liquid which contains a combination of humectant, propylene glycol (PG), vegetable glycerin (VG), flavorings, and nicotine. For optimal effectiveness of the e-cigarettes, the e-liquid requires to be heated and under high temperature conditions, chemical reactions may result in the formation of new harmful compounds such as carbonyl compounds, which is mainly attributed to PG. Therefore, the aim of this research project was to develop PG free nicotine containing e-liquid and investigating the use of PG free e-liquid for fluticasone propionate (FP) application using vaping devices. In this work, UV-VIS spectroscopic method for the analysis of nicotine and FP (as model drug) were employed and validated according to the ICH guidelines, the e-liquid formulas were prepared using Various surfactants (tween 80, tween 20, span 20, and oleic acid) were investigated at various concentrations. Produced formulations were characterized for solubility and appearance, and optimal formulations were further analyzed for aerodynamic performance using the next generation impactor (NGI) and Fourier Transform infrared (FTIR). Results revealed the superiority of tween 80 in solubilizing nicotine and FP. The aerodynamic performance of nicotine containing eliquid were evaluated using four key parameters: a) emitted dose (% ED), b) respirable dose (RD), c) fine particles fraction of emitted dose and d) theoretical dose FPFED and FPFTD, respectively. In comparison between prepared formulations and a marketed product, the results demonstrated the ability of PG free e-liquid to produce higher ED (98.44%) for F1 vs 88.51% for the marketed products. Similarly, the RD of F1 was 802.44 µg while only 450.65 µg for the marketed product. NGI results of FP revealed comparable and even significantly superior results when compared with the marketed pressurized metered dose inhaler (PMDI) aerodynamic parameters (one-way ANOVA p=0.041). PG free FP e-liquid produced %ED of 97.33% vs 88.26% for marketed pMDI, RD of 67.07 µg vs 44.65 µg for the marketed product. Overall, this work provided evidence of the capability of vaping devices to successfully deliver PG free nicotine and FP, that was employed as a model drug, to the lower parts of the lungs. However, further studies need to be investigated to assess the long-term stability and safety of the optimal formulations