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. 2022 Nov 17;8(11):746.
doi: 10.3390/gels8110746.

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

Hassan Raza  1 , Shefaat Ullah Shah  2 , Zakir Ali  1 , Atif Ullah Khan  1 , Irfa Basharat Rajput  1 , Arshad Farid  3 , Mohammed Al Mohaini  4   5 , Abdulkhaliq J Alsalman  6 , Maitham A Al Hawaj  7 , Saima Mahmood  2 , Abid Hussain  8 , Kifayat Ullah Shah  1
Affiliations

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

Hassan Raza et al. Gels. .

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.

Keywords: acitretin; bioavailability; entrapment efficiency; fluocinolone acetonide; nanostructured lipid carrier; occlusive effect.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Desirability and point prediction data provided by Design Expert® for the selection of the optimized formulation.
Figure 2
Figure 2
3D response surface graphs: effects of lipids, surfactants and drugs on particle size (a–c); zeta potential (d–f): % entrapment efficiency of acitretin (g–i): % entrapment efficiency of fluocinolone (j–l).
Figure 2
Figure 2
3D response surface graphs: effects of lipids, surfactants and drugs on particle size (a–c); zeta potential (d–f): % entrapment efficiency of acitretin (g–i): % entrapment efficiency of fluocinolone (j–l).
Figure 3
Figure 3
Particle characterization: (a) particle size and PDI analysis; (b) zeta potential analysis; (c) TEM analysis.
Figure 3
Figure 3
Particle characterization: (a) particle size and PDI analysis; (b) zeta potential analysis; (c) TEM analysis.
Figure 4
Figure 4
XRD analysis of acitretin, fluocinolone, stearic acid and lyophilized optimized FLU–ACT-coloaded NLCs.
Figure 5
Figure 5
DSC analyses of fluocinolone, acitretin and optimized FLU–ACT-coloaded NLCs.
Figure 6
Figure 6
FTIR analysis of fluocinolone, acitretin, stearic acid, oleic acid and lyophilized FLU–ACT-coloaded NLCs.
Figure 7
Figure 7
Histopathological analysis of: (a) positive control; (b) FLU–ACT–coloaded NLC treatment; (c) negative control.
Figure 8
Figure 8
In vitro release profiles of fluocinolone at (a) pH of 5.5 and (b) pH of 7.4, and acitretin at (c) pH of 5.5 and (d) pH of 7.4.
Figure 9
Figure 9
Ex vivo permeability data of FLU–ACT-coloaded NLC gel and FLU–ACT conventional gel.
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