Clobetasol-loaded core-active lipid nanoparticles: an enhanced therapy for inflammatory skin conditions

Clobetasol propionate (CP) is a high-potency corticosteroid drug used for the symptomatic treatment of inflammatory skin conditions such as psoriasis and atopic dermatitis, which affect around 10 % of the global population. Despite its proven efficacy in the short-term management of the mild manifestations of this disease, long term treatment is limited due to its high skin permeation causing systemic adverse effects. To overcome these limitations and improve its efficacy, the aim of this work was to develop and optimize core-active nanostructured lipid carriers (NLC) encapsulating CP (CP-NLC). In addition to encapsulating CP, the NLC matrix contained lavender and peppermint oil, which confer them intrinsic activity against psoriasis such as anti-inflammatory properties. CP-NLC were developed using the high-pressure homogenization method. The optimized CP-NLC showed an average size below 200 nm with a monomodal distribution, a zeta potential around -15 mV and an encapsulation efficiency greater than 95 %. Moreover, the formulation was stable up to 60 days and released CP in a sustained manner. In addition, CP-NLC showed a 2.85-fold higher retention in skin tissue of CP than the conventional cream with no increased permeation. CP-NLC significantly reduced angiogenesis while remaining non-toxic, rapidly internalized into keratinocytes and provided sustained NF-κB inhibition beyond free clobetasol, indicating an enhancement of anti-inflammatory and anti-angiogenic activity of clobetasol and core-active carriers. As a conclusion, CP-NLC were successfully developed and may constitute a promising alternative for the treatment of inflammatory skin diseases.