Effervescent cannabidiol solid dispersion-doped dissolving microneedles for boosted melanoma therapy via the “TRPV1-NFATc1-ATF3” pathway and tumor microenvironment engineering

Jiachen Shi; Qiuling Ma; Wenting Su; Congyan Liu; Huangqin Zhang; Yuping Liu; Xiaoqi Li; Xi Jiang; Chang Ge; Fei Kong; Yan Chen; Ding Qu

doi:https://doi.org/10.1186/s40824-023-00390-x

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자료유형: 학술저널

저자정보: Jiachen Shi (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Qiuling Ma (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Wenting Su (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Congyan Liu (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Huangqin Zhang (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Yuping Liu (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Xiaoqi Li (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Xi Jiang (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Chang Ge (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Fei Kong (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Yan Chen (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine) Ding Qu (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine)

저널정보: 한국생체재료학회 생체재료학회지 생체재료학회지 제27권

발행연도: 2023.3

수록면: 1,343 - 1,357 (15page)

DOI: https://doi.org/10.1186/s40824-023-00390-x

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Background Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration. Methods In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO3 & NaHCO3) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the “one-step micro-molding” method for boosted transdermal and tumoral delivery of cannabidiol (CBD). Results Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca2+ influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca2+ can not only amplify the effervescent effect but also provide sufficient Ca2+ with CBD to potentiate the anti-melanoma efficacy. Such a “one stone, two birds” strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo. Conclusions This study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.

#Dissolving microneedles #Melanoma #Cannabidiol #Effervescent #Tumor microenvironment #Ca2+ influx

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