Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution.

Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.