Laser-assisted nanocarrier delivery to achieve cutaneous siRNA targeting for attenuating psoriasiform dermatitis

Woan Ruoh Lee, Wei Ling Chou, Zih Chan Lin, Calvin T. Sung, Chien Yu Lin, Jia You Fang

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Psoriasis is an autoimmune skin disorder presenting the excessive expression of interleukin (IL)-6. The topical use of small interfering RNA (siRNA) has been increasingly discovered for treating skin diseases. A delivery system capable of protecting siRNA while facilitating both skin targeting and cellular entrance is critical for the successful medication of topically-applied siRNA. Herein, we developed a delivery system for siRNA based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles and combined this system with an ablative laser to promote skin absorption for topical psoriasis therapy. The siRNA absorption enhancement was compared by two laser modalities: a fractional CO2 laser and a fully-ablative Er:YAG laser. We characterized the effect of the delivery system by the cellular uptake, IL-6 silencing, in vitro skin absorption, cutaneous biodistribution, and in vivo psoriasiform dermatitis in mice. The nanocarriers showed minimal cytotoxicity and facile cellular uptake to knock down the IL-6 expression. The nanoformulation containing a cationic surfactant (Forestall) for ion pairing with siRNA achieved a 66% and 77% IL-6 knockdown efficiency toward keratinocytes and macrophages, respectively. In the Franz cell absorption, the lasers increased the naked siRNA penetration to the receptor compartment by 3.7–5.0-fold but remarkably reduced skin deposition using imiquimod (IMQ)-treated psoriasiform skin as the barrier. The fractional laser facilitated nanoparticle-associated siRNA skin deposition up to 3.3-fold, whereas the transport of the nanocarriers to the receptor was negligible. Qualitatively, the lasers increased nanoparticle delivery in the epidermis with limited effect to elevate the penetration depth. The fractional-mediated nanocarrier delivery dramatically attenuated the erythema and scaly lesions of psoriasiform dermatitis. The histological examination displayed a reduction of epidermal hyperplasia and macrophage infiltration by the combination of laser and nanosystem. The passive and laser-assisted naked siRNA delivery was less effective in mitigating dermatitis. The topical delivery of fractional laser-assisted nanoparticles on mice resulted in a 56% IL-6 knockdown. Our results manifested the benefit of cutaneous siRNA targeting using ablative lasers to deliver nanocarriers for treating psoriatic inflammation.
原文英語
頁(從 - 到)590-606
頁數17
期刊Journal of Controlled Release
347
DOIs
出版狀態已發佈 - 7月 2022

ASJC Scopus subject areas

  • 藥學科學

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