Nucleic acid delivery into skin for the treatment of skin disease: Proofs-of-concept, potential impact, and remaining challenges

Abstract

Nucleic acids (NAs) hold significant potential for the treatment of several diseases. Topical delivery of NAs for the treatment of skin diseases is especially advantageous since it bypasses the challenges associated with systemic administration which suffers from enzymatic degradation, systemic toxicity and lack of targeting to skin. However, the skin’s protective barrier function limits the delivery of NAs into skin after topical application. Here, we highlight strategies for enhancing delivery of NAs into skin, and provide evidence that translation of topical NA therapies could have a transformative impact on the treatment of skin diseases.

Therapeutic RNAi robed with ionic liquid moieties as a simple, scalable prodrug platform for treating skin disease

“…In addition, robed-siRNA properties and behavior are independent of siRNA sequence. This opens up the possibilities of using robed-siRNAs for the treatment of myriad other skin diseases for which known protein knockdown targets exist such as psoriasis, atopic dermatitis, skin cancer, melasma, pachyonychia congenita, and many others [2]. Further, this opens up the possibility for more effective treatments through the use robed-siRNA cocktails that knockdown several protein targets simultaneously.…”

“…cellulite, wrinkling, and brown spots) to debilitating and even deadly ( e.g. severe pain, skin barrier disruption, dehydration, and systemic infection) [2]. High prevalence of skin disease and outward presentation of symptoms combined with high rates of morbidity and mortality associated with severe skin disease results in significant physical, emotional, and economic burden [1, 3].…”

“…Advantages of topical siRNA delivery include direct access to the diseased site, easy observation of treatment progress, easy observation and excision of sites of adverse reaction, sustained and controlled drug delivery, and potent and specific knockdown of causative proteins [2]. Further, topical application avoids drug degradation in the GI tract and limits systemic toxicity and drug clearance from the diseased tissue [5, 6].…”

Nanodispersões de fase líquido-cristalina como carreadoras de siRNA no tratamento tópico da psoríase: Avaliação em modelos in vitro e in vivo

“…Doenças cutâneas relacionadas a reações inflamatórias (vitiligo, psoríase e dermatite atópica), ao comportamento anormal das células (carcinoma espinocelular e melanoma), dano (queimadura e ferida) e doenças de pele monogênicas (paquioníquia congênita) são de grande interesse para a terapia com siRNAs, pois apresentam alvos moleculares bem definidos que podem ser silenciados, resultando em benefícios terapêuticos (THANIK et al, 2007;HICKERSON et al, 2008;TRAN et al, 2008;JAKOBSEN et al, 2009;KIGASAWA et al, 2010 FOUGEROLLES, 2008;GEUSENS et al, 2011;ZAKREWSKY;MITRAGOTRI, 2015;DESMET et al, 2016).…”

“…As principais estratégias para a liberação de siRNAs na pele incluem o uso de formulações (lipossomas, nanopartículas lipídicas, nanopartículas poliméricas, peptídeos, dentre outras), métodos químicos (promotores de absorção cutânea) e os métodos físicos (iontoforese, sonoforese, microagulhas, eletroporação, dentre outrosw) com a finalidade de reduzir as propriedades de barreira da pele, promover a penetração cutânea e a utilização dessa macromolécula no tratamento de doenças de pele (PAUDEL et al, 2010;GEUSENS et al, 2011;VICENTINI et al, 2013a;ZAKREWSKY;MITRAGOTRI, 2015).…”