In Vitro and Ex Vivo Evaluation of Fluocinolone Acetonide–Acitretin-Coloaded Nanostructured Lipid Carriers for Topical Treatment of Psoriasis

Abstract

Psoriasis is chronic autoimmune disease that affects 2–5% of the global population. Fluocinolone acetonide (FLU) and acitretin (ACT) are widely used antipsoriatic drugs that belong to BCS classes II and IV, respectively. FLU exhibits side effects, such as skin irritation and a burning sensation. ACT also shows adverse effects, such as gingivitis, teratogenic effects and xerophthalmia. In the present study, topical nanostructured lipid carriers (NLCs) were fabricated to reduce the side effects and enhance the therapeutic efficacy. FLU–ACT-coloaded NLCs were prepared by the modified microemulsion method and optimized by the Box–Behnken model of Design Expert® version 12. The optimization was based on the particle size (PS), zeta potential (ZP) and percentage of encapsulation efficiency (%EE). The physicochemical analyses were performed by TEM, FTIR, XRD and DSC to assess the morphology, chemical interactions between excipients, crystallinity and thermal behavior of the optimized FLU–ACT-coloaded NLCs. The FLU–ACT-coloaded NLCs were successfully loaded into gel and characterized appropriately. The dialysis bag method and Franz diffusion cells were used for the in vitro release and ex vivo permeation studies, respectively. The optimized FLU–ACT-coloaded NLCs had the desired particle size of 288.2 ± 2.3 nm, ZP of −34.2 ± 1.0 mV and %EE values of 81.6 ± 1.1% for ACT and 75 ± 1.3% for FLU. The TEM results confirmed the spherical morphology, while the FTIR results showed the absence of chemical interactions of any type among the ingredients of the FLU–ACT-coloaded NLCs. The XRD and DSC analyses confirmed the amorphous nature and thermal behavior. The in vitro study showed the sustained release of the FLU and ACT from the optimized FLU–ACT-coloaded NLCs and FLU–ACT-coloaded NLC gel compared with the FLU–ACT suspension and conventional gel. The ex vivo study confirmed the minimal permeation of both drugs from the FLU–ACT-coloaded NLC gel.

Recent Approaches for the Topical Treatment of Psoriasis Using Nanoparticles

“…The ex vivo penetration study demonstrated lower permeation for the NLC gel co-formulated with fluocinolone acetonide and acitretin in comparison to the conventional fluocinolone acetonide and acitretin-containing gel. On the other hand, the skin deposition for the NLC formulation was greater than that of the conventional gel, verifying that NLCs were present in the deeper skin layers [ 112 ]. Table 4 summarizes the above-mentioned NLCs and their characteristics.…”

Biocompatible lipid nanocarriers for improved skin delivery of fluocinolone acetonide: Physicochemical and in vitro performances

“…Although there are several conventional topical products with FA on the market, physical difficulties in applying the treatment, lack of visible effect, and, most importantly, numerous side effects lead to poor patient adherence and limit their efficacy. As a result, intensive research has concentrated on the design of nanotechnology-based drug delivery systems to ensure targeted delivery to the skin and enhance the benefit-risk ratio of topical corticosteroids such as FA (4)(5)(6).…”