期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 160, 期 -, 页码 704-714出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2017.10.029
关键词
Psoriasis; Curcumin; Silk fibroin; Permeable nanoparticles; Drug delivery systems; Topical; Skin permeation
资金
- National Natural Science Foundation of China [81603036, 81571392]
- Zhejiang provincial program for the cultivation of high-level innovative health talents
- 151 talent project of Zhejiang province
- 551 talent project of Wenzhou
- key support of high level talent innovation and technology project of Wenzhou
- Wenzhou Bureau of Science and Technology [Y2014730]
- Wenzhou Medical University [QTJ15020]
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-alpha-tocopheryl succinate-grafted-epsilon-polylysine conjugate (VES-g-epsilon-PLL) was synthesized and self-assembled into polymeric nanoparticles. The nanoparticles of VES-g-epsilon-PLL exhibiting an ultra small hydrodynamic diameter (24.4 nm) and a positive Zeta potential (19.6 mV) 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-alpha, NF-kappa B 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. (C) 2017 Published by Elsevier B.V.
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