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Exploring the potential for rosacea therapeutics of siRNA dispersion in topical emulsions.

Exp Dermatol. 2019 Jan 16;:

Authors: Colombo S, Harmankaya N, Water JJ, Bohr A

Abstract
Rosacea is a prevalent skin condition dependent on the individual genetic profile. The current pharmacological management of this condition is mostly based on small molecule drugs predominately effective in ameliorating the inflammatory condition. Emerging molecular approaches could present an opportunity for managing rosacea conditions at transcriptomic level, and in the future allow personalized approaches. RNA medicines, such as small RNA interference (siRNA), could provide a flexible and applicable tool reaching this aim. However, the topical siRNA delivery by dermatological emulsions, commonly used in the daily management of rosacea, is still largely unexplored. Consequently, RNA interference application to rosacea was defined on molecular bases by genetic expression meta-data analysis. Based on this, an siRNA directed against TLR2 was designed and validated in vitro on murine macrophages and fibroblasts. Next, siRNA was dispersed in the continuous phase of emulsions and was characterized for commonly used dermatologic bases. Finally, the potential delivery performance of the topical emulsions was tested in vivo on healthy Balb/c mice. It was found that the interaction of siRNA with combination of excipients such as urea and glycerol, is likely to favor the siRNA delivery, inducing genetic silencing of TLR2. These findings provide a foundation for the future development of topical RNA-based dispersions for topical molecular medicines, by emphasizing on the formulation and therapeutic-based opportunities with dermatological treatments. This article is protected by copyright. All rights reserved.

PMID: 30650201 [PubMed - as supplied by publisher]

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