Epigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks, including stability issues, low bioavailability, and a short half-life. Therefore, the purpose of this research was to develop and optimize an inhalable EGCG nano-liposome formulation aiming to overcome EGCG’s drawbacks by applying a design of experiments strategy. The aerodynamic behaviour of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-β pathway were determined using a cell-based reporter assay. The newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a polydispersity index (PDI) of 0.18, a zeta potential of −25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results are in complete agreement with the predicted values of the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, the fine particle fraction (FPF) was 53.46%, and the percentage of particles equal to or less than 3 µm was 34.3%. This demonstrates that the novel EGCG liposome has all the properties required to be inhalable, and it is expected to be deposited deeply in the lung. The TGFβ pathway is activated in PAH lungs, and the optimum EGCG nano-liposome inhibits TGFβ signalling in cell-based studies and thus holds promise as a potential treatment for PAH.