Solid lipid nanoparticles (SLNs) can enhance drug penetration into the skin,
yet the mechanism of the improved transport is not known in full. To unravel
the influence of the drug-particle interaction on penetration enhancement, 3
glucocorticoids (GCs), prednisolone (PD), the diester prednicarbate (PC) and
the monoester betamethasone 17-valerate (BMV), varying in structure and
lipophilicity, were loaded onto SLNs. Theoretical permeability coefficients
(cm/s) of the agents rank BMV (–6.38) ≧ PC (–6.57) > PD (–7.30). GC-particle
interaction, drug release and skin penetration were investigated including a
conventional oil-in-water cream for reference. Both with SLN and cream, PD
release was clearly superior to PC release which exceeded BMV release. With
the cream, the rank order did not change when studying skin penetration, and
skin penetration is thus predominantly influenced by drug release. Yet, the
penetration profile for the GCs loaded onto SLNs completely changed, and
differences between the steroids were almost lost. Thus, SLNs influence skin
penetration by an intrinsic mechanism linked to a specific interaction of the
drug-carrier complex and the skin surface, which becomes possible by the lipid
nature and nanosize of the carrier and appears not to be derived by testing
drug release. Interestingly, PC and PD uptake from SLN even resulted in
epidermal targeting. Thus, SLNs are not only able to improve skin penetration
of topically applied drugs, but may also be of particular interest when
specifically aiming to influence epidermal dysfunction
