An elastic liposomal formulation for RNAi-based topical treatment of skin disorders: Proof-of-concept in the treatment of psoriasis

被引:61
作者
Desmet, Eline [1 ]
Bracke, Stefanie [1 ]
Forier, Katrien [2 ,3 ]
Taevernier, Lien [4 ]
Stuart, Marc C. A. [5 ]
De Spiegeleer, Bart [4 ]
Raemdonck, Koen [2 ]
Van Gele, Mireille [1 ]
Lambert, Jo [1 ]
机构
[1] Univ Ghent, Dept Dermatol, B-9000 Ghent, Belgium
[2] Univ Ghent, Dept Pharmaceut, B-9000 Ghent, Belgium
[3] Univ Ghent, Ctr Nano & Biophoton, B-9000 Ghent, Belgium
[4] Univ Ghent, Dept Pharmaceut Anal, B-9000 Ghent, Belgium
[5] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Electron Microscopy, Groningen, Netherlands
关键词
Lipid-based nanoparticle; Skin disorder; RNA interference; Liposome; Topical drug delivery; Gene therapy; CELL-PENETRATING PEPTIDES; IN-VITRO; TRANSFECTION EFFICIENCY; NONVIRAL VECTOR; DERMAL DELIVERY; SIRNA DELIVERY; GENE-TRANSFER; PLASMID DNA; CARRIERS; ETHOSOMES;
D O I
10.1016/j.ijpharm.2016.01.042
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
RNA interference (RNAi) is a rapidly emerging approach for targeted gene silencing to alleviate disease pathology. However, lack of efficient carriers for targeted delivery delays the clinical translation of RNAi. An interesting target for local RNAi therapeutics is the skin as it allows direct access to target cells. Still, applications are limited due to the effective skin barrier which hinders penetration. Herein, a description is given of a liposomal carrier, called 'DDC642', capable of delivering RNAi molecules to the epidermis of impaired and intact human skin, without targeting the dermis or circulatory system. In a psoriasis tissue model, down-regulation of the psoriasis marker human beta-defensin 2 by DDC642-delivered siRNA was confirmed, providing proof-of-concept. These liposomes thus hold great potential as topical delivery system for RNAi therapeutics in the treatment of numerous skin diseases. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:268 / 274
页数:7
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