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

详细信息    查看全文

• 作者：Eline Desmet^a ; ^{eline.desmet@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Stefanie Bracke^a ; ^{stefanie.bracke@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Katrien Forier^b ; ^c ; ^{katrien.forier@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Lien Taevernier^d ; ^{lien.taevernier@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Marc C.A. Stuart^e ; ^{m.c.a.stuart@rug.nl" class="auth_mail" title="E-mail the corresponding author} ; Bart De Spiegeleer^d ; ^{bart.despiegeleer@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Koen Raemdonck^b ; ^{koen.raemdonck@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Mireille Van Gele^a ; ¹ ; ^{mireille.vangele@ugent.be" class="auth_mail" title="E-mail the corresponding author} ; Jo Lambert^a ; ¹ ; ^{jo.lambert@uzgent.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：SEC ; SECosomes ; HiP ; HiPerfect ; LPX ; lipoplex ; DOTAP ; 2 ; 3-dioleoyloxy-propyl-trimethylammoniumchloride ; DOPE ; 1 ; 2-dioleoyl-sn-glycero-3-phosphoethanolamine ; DS ; dextran sulphate ; KC ; keratinocyte ; MC ; melanocyte ; DEFB4 ; defensing beta 4 ; hBD-2 ; human beta-defensin 2
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：16 March 2016
• 年：2016
• 卷：500
• 期：1-2
• 页码：268-274
• 全文大小：1484 K

文摘

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.