Study and Evaluation of the Potential of Lipid Nanocarriers for Transdermal Delivery of siRNA.,Biotechnology Journal

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Study and Evaluation of the Potential of Lipid Nanocarriers for Transdermal Delivery of siRNA.
Biotechnology Journal ( IF 3.2 ) Pub Date : 2020-07-17 , DOI: 10.1002/biot.202000079
Kyungwoo Lee _{1,

2} , Daejin Min _{3,

4} , Yonghyun Choi ₁ , Jiwon Kim ₁ , Semi Yoon ₁ , Jaehee Jang ₁ , Soomin Park ₅ , Masayoshi Tanaka ₆ , Yong Woo Cho ₄ , Hyung-Jun Koo ₇ , Hojeong Jeon ₂ , Jonghoon Choi ₁

Affiliation

The topical delivery of siRNA‐based therapies has opened new avenues for the treatment of skin disorders. The use of siRNA as a therapeutic, however, is limited due to its rapid degradation and poor cellular uptake. Furthermore, the top layer of skin, the stratum corneum, is a major barrier to the delivery of topical agents. There is an unmet need for efficient topical formulations for delivering siRNA to the site of action. In this study, 1,2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) or lipofectamine is used to prepare a nanocarrier for delivering siRNA against glyceraldehyde 3‐phosphate dehydrogenase (GAPDH); GAPDH expression is then evaluated at the cellular level. In addition, a dermal transport assay is designed and implemented to evaluate the penetration and delivery efficacy of siRNA in pig skin using lipid nanocarriers. The delivery of siRNA with the use of a lipid nanocarrier is significantly better than the delivery of siRNA without it. Thus, the findings identify lipid nanocarriers as excellent candidates for the transdermal delivery of siRNA for gene silencing in the skin and thus for applications in related preclinical models.

中文翻译：

脂质纳米载体对siRNA透皮递送的潜力的研究和评估。

基于siRNA的局部治疗为皮肤病的治疗开辟了新途径。但是，由于siRNA的快速降解和较差的细胞摄取，其用途有限。此外，皮肤的顶层，角质层，是局部用药递送的主要障碍。对于将siRNA递送至作用部位的有效局部制剂存在未满足的需求。在这项研究中，使用1,2-二油酰基-3-三甲基铵-丙烷（DOTAP）或lipofectamine制备纳米载体，以递送针对甘油三磷酸甘油醛脱氢酶（GAPDH）的siRNA。然后在细胞水平评估GAPDH表达。另外，设计并实施了皮肤转运测定法，以使用脂质纳米载体评估siRNA在猪皮肤中的渗透和递送功效。使用脂质纳米载体递送siRNA明显优于不使用脂质纳米载体递送siRNA。因此，这些发现确定脂质纳米载体是用于siRNA的透皮递送以在皮肤中使基因沉默并因此用于相关临床前模型中的极好的候选者。

更新日期：2020-07-17

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