Skin-penetrating polymeric nanoparticles incorporated in silk fibroin hydrogel for topical delivery of curcumin to improve its therapeutic effect on psoriasis mouse model

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2017-12, Vol.160, p.704-714
• Main Authors: Mao, Kai-Li, Fan, Zi-Liang, Yuan, Jian-Dong, Chen, Pian-Pian, Yang, Jing-Jing, Xu, Jie, ZhuGe, De-Li, Jin, Bing-Hui, Zhu, Qun-Yan, Shen, Bi-Xin, Sohawon, Yasin, Zhao, Ying-Zheng, Xu, He-Lin
• Format: Article
• Language: English
• Subjects: Curcumin; Drug delivery systems; Permeable nanoparticles; Psoriasis; Silk fibroin; Skin permeation; Topical
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2017.10.029

VES-g-ε-PLL nanoparticle with skin-penetrating ability was incorporated into silk fibroin hydrogel to improve therapeutic effect of curcumin on psoriasis mouse. [Display omitted] •VES-g-PLL nanoparticle was incorporated into SF solution, gelation of which was not compromised under sonication.•The skin-penetrating ability of curcumin against the thicking corneum of psoriatic mice was enhanced by CUR-NPs-gel.•The therapeutic effect of CUR-NPs-gel on psoriatic mice was highly associated with inhibition of skin inflammation. A poor percutaneous penetration capability for most topical anti-inflammatory drugs is one of the main causes compromising their therapeutic effects on psoriatic skin. Even though curcumin has shown a remarkable efficacy in the treatment of psoriasis, its effective penetration through the stratum corneum is still a major challenge during transdermal delivery. The aim of our study was to design skin-permeating nanoparticles (NPs) to facilitate delivery of curcumin to the deeper layers of the skin. A novel amphiphilic polymer, RRR-α-tocopheryl succinate-grafted-ε-polylysine conjugate (VES-g-ε-PLL) was synthesized and self-assembled into polymeric nanoparticles. The nanoparticles of VES-g-ε-PLL exhibiting an ultra-small hydrodynamic diameter (24.4nm) and a positive Zeta potential (19.6mV) provided a strong skin-penetrating ability in vivo. Moreover, curcumin could effectively be encapsulated in the polymeric nanoparticles with a drug loading capacity of 3.49% and an encapsulating efficiency of 78.45%. In order to prolong the retention time of the ultra-small curcumin-loaded nanoparticles (CUR-NPs) in the skin, silk fibroin was used as a hydrogel-based matrix to further facilitate topical delivery of the model drug. In vitro studies showed that CUR-NPs incorporated in silk fibroin hydrogel (CUR-NPs-gel) exhibited a slower release profile of curcumin than the plain CUR-gel, without compromising the skin penetration ability of CUR-NPs. In vivo studies on miquimod-induced psoriatic mice showed that CUR-NPs-gel exhibited a higher therapeutic effect than CUR-NPs as the former demonstrated a more powerful skin-permeating capability and a more effective anti-keratinization process. CUR-NPs-gel was therefore able to inhibit the expression of inflammatory cytokines (TNF-α, NF-κB and IL-6) to a greater extent. In conclusion, the permeable nanoparticle-gel system may be a potential carrier for the topical delivery of lipophilic anti-psoriatic drugs.