Technological advances in lipid vesicles facilitate optimization of their properties to achieve therapeutic goals and promote alternative drug administration routes. Sildenafil citrate (SC) is orally administered for the treatment of pulmonary hypertension, but local release would be advantageous in terms of efficacy and safety. In the present study, liposomes from egg phosphatidylcholine and cholesterol loaded with SC, with and without d-α-tocopheryl polyethylene glycol 1000 succinate (Vit E TPGS), were prepared by sonication of the components. A transmembrane pH gradient was applied for active loading of liposomes, and the size, zeta potential, and entrapment efficiency (EE%) were determined. The liposomes were lyophilized and then nebulized. The nebulized samples were collected and the EE% was determined. The transmembrane pH gradient produced a significant increase in the EE% (from 17.68 ± 4.25% to 89.77 ± 7.64%) and, after lyophilization, the EE% remained the same as that of the originals, but the size and zeta potential were modified. EE% of liposomes decreased upon nebulization, particularly for those with Vit E TPGS. Thus, the additives used for lyoprotection reduced the impact of nebulization. Additional studies are essential, but according to these results, SC-loaded liposomes can be considered as suitable and safe carriers for the local release of sildenafil in the pulmonary system.