pH-sensitive nonionic surfactant vesicles (niosomes) by polysorbate-20 
(Tween-20) or polysorbate-20 derivatized by glycine (added as pH sensitive 
agent), were developed to deliver Ibuprofen (IBU) and Lidocaine (LID). For the 
physical-chemical characterization of vesicles (mean size, size distribution, 
zeta potential, vesicle morphology, bilayer properties and stability) dynamic 
light scattering (DLS), small angle X-ray scattering and fluorescence studies 
were performed. Potential cytotoxicity was evaluated on immortalized human 
keratinocyte cells (HaCaT) and on immortalized mouse fibroblasts Balb/3T3. In 
vivo antinociceptive activity (formalin test) and anti-inflammatory activity 
tests (paw edema induced by zymosan) in murine models were performed on 
drug-loaded niosomes. pH-sensitive niosomes were stable in the presence of 0 and 
10% fetal bovine serum, non-cytotoxic and able to modify IBU or LID 
pharmacological activity in vivo. The synthesis of stimuli responsive 
surfactant, as an alternative to add pH-sensitive molecules to niosomes, could 
represent a promising delivery strategy for anesthetic and anti-inflammatory 
drugs.