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  • Title: Coated microneedles mediated intradermal delivery of octaarginine/BRAF siRNA nanocomplexes for anti-melanoma treatment.
    Author: Ruan W, Zhai Y, Yu K, Wu C, Xu Y.
    Journal: Int J Pharm; 2018 Dec 20; 553(1-2):298-309. PubMed ID: 30347273.
    Abstract:
    BRAF is the most frequently mutated gene in skin melanoma. Applying BRAF siRNA (siBraf) to silencing BRAF gene is a current frontline therapy for melanoma. However, delivery of macromolecular siRNA into the tumor site and introduction of siRNA into the tumor cells remain as challenges. In this study, we for the first time developed a siBraf delivery system based on cell penetrating peptide octaarginine (R8) nanocomplexes combined with coated microneedles (MNs), i.e. R8/siBraf coated MNs, for targeted anti-melanoma treatment. The R8/siBraf nanocomplexes were optimized based on the internalization of siBraf by A375 cells. In vitro A375 cell experiments presented that R8/siBraf can enhance siBraf transfection, silence BRAF gene, and inhibit tumor cells growth, comparable to polyethylenimine (PEI)/siBraf. R8/siBraf coated MNs can effectively deliver R8/siBraf into the disease site. In vivo anti-melanoma experiments indicated that R8/siBraf coated MNs can significantly inhibit the melanoma development, induce the tumor cells apoptosis, and suppress their proliferation. The BRAF gene in tumor were also significantly silenced in vivo. SiBraf intradermal delivery via combining MNs and R8 nanocomplexes is a promising approach for skin melanoma treatment, which exploited both virtues of MNs and cell penetrating peptide to obtain the targeting inhibition efficacy on skin melanoma.
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