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

Hassan Raza; Shefaat Ullah Shah; Zakir Ali; Atif Ullah Khan; Irfa Basharat Rajput; Arshad Farid; Mohammed Al Mohaini; Abdulkhaliq J Alsalman; Maitham A Al Hawaj; Saima Mahmood; Abid Hussain; Kifayat Ullah Shah

doi:10.3390/gels8110746

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

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

Authors

Affiliations

¹ Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Aam University, Islamabad 45230, Pakistan.
² Faculty of pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan.
³ Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan.
⁴ Basic Sciences Department, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Alahsa 31982, Saudi Arabia.
⁵ King Abdullah International Medical Research Center, Alahsa 31982, Saudi Arabia.
⁶ Department of Clinical Pharmacy, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
⁷ Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Ahsa 31982, Saudi Arabia.
⁸ Department of Pharmacy, Faculty of Medical and Health Sciences, University of Poonch Rawalakot, Rawalakot 12350, Pakistan.

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.

Grants and funding

This research received no external funding.