The aim of this study was to develop new solid lipid nanoparticles of isotretinoin (IT-SLNs) and evaluate the ability of IT-SLNs to improve photostability, reduce skin permeation and irritating effects. IT-SLNs were prepared by the hot high pressure homogenization method. Size, zeta potential and morphological characteristics of the preparations were assessed by transmission electron microscopy (TEM) and thermotropic properties with differential scanning calorimetry (DSC). IT-SLNs had a small average diameter of 74.05 ± 8.91 nm and high encapsulation efficiency (EE) of 80.6 ± 1.2 %. The results showed that the entrapment of IT into SLNs reduced significantly its photodegradation. The