The hot lipid phase produced was dispersed in a 1/3(28.77 g) of the aqueous solution of hydrophilic surfactant (Tween80) prepared by weighing out 1.67 g Tween 80 heated at the sametemperature and sonicated by using a probe sonicator (Bandelinsonopuls, Berlin, Germany) for 5 min (Model HD 3200, Prob TT25,50% power and 19.82 KJ) to form a coarse pre-emulsion. At the endof the sonication, the mixture was dispersed into the remaining 2/3of the hydrophilic surfactant solution (containing 3.33 g Tween 80)maintained in an ice bath. The final mixture was sonicated againfor 10 min (50% power and 51.77 KJ) whilst still immersed in theice-bath. This cooling step promoted the formation of the lipidnanoparticles. SP-NLC dispersion was incorporated into 1% w/vCarbopol gel containing 0.2 g methyl paraben as preservative. Theobtained gel was allowed to hydrate for 24 h. The resulting mixturewas then stirred followed by neutralization with tri-ethanolamine(approximately 10 drops) to obtain an adequate semisolid carbopolgel matrix (for a full composition of each formulation refer to Table1S in the Supplementary material).