Comparison of normal versus imiquimod-induced psoriatic skin in mice for penetration of drugs and nanoparticles

Abstract

Lin Sun,1,2 Zeyu Liu,1 Zibei Lin,1 Dongmei Cun,3 Henry HY Tong,4 Ru Yan,1 Ruibing Wang,1 Ying Zheng1 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region, People’s Republic of China; 2Department of Pharmaceutical Sciences, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, 519041, People’s Republic of China; 3Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, People’s Republic of China; 4School of Health Sciences, Macao Polytechnic Institute, Macao Special Administrative Region, People’s Republic of China Background: As an immune-mediated skin disease, psoriasis encounters therapeutic challenges on topical drug development due to the unclear mechanism, and complicated morphological and physiological changes in the skin. Methods: In this study, imiquimod-induced psoriatic mouse skin (IMQ-psoriatic skin) was chosen as the in vitro pathological model to explore the penetration behaviors of drugs and nanoparticles (NPs). Results: Compared with normal skin, significantly higher penetration and skin accumulation were observed in IMQ-psoriatic skin for all the three model drugs. When poorly water-soluble curcumin was formulated as NPs that were subsequently loaded in gel, the drug’s penetration and accumulation in both normal and IMQ-psoriatic skins were significantly improved, in comparison with that of the curcumin suspension. Interestingly, the NPs’ size effect, in terms of their penetration and accumulation behaviors, was more pronounced for IMQ-psoriatic skin. Furthermore, by taking three sized FluoSpheres® as model NPs, confocal laser scanning microscopy demonstrated that the penetration pathways of NPs no longer followed the hair follicles channels, instead they were more widely distributed in the IMQ-psoriatic skin. Conclusion: In conclusion, the alternation of the IMQ-psoriatic skin structure will lead to the enhanced penetration of drug and NPs, and should be considered in topical drug formulation and further clinical practice for psoriasis therapy. Keywords: imiquimod-induced psoriatic skin, pathological model, topical delivery, penetration, nanoparticles

Keywords

• Imiquimod-induced Psoriatic skin
• Pathological model
• Topical delivery
• Penetration
• Nanoparticles