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

Biomaterials Research

Research Article

Wenting Su¹  Fei Kong¹  Xi Jiang¹  Qiuling Ma¹  Jiachen Shi¹  Chang Ge¹  Congyan Liu²  Huangqin Zhang²  Xiaoqi Li²  Yan Chen²  Ding Qu²  Yuping Liu² 

[1] Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 210028, Nanjing, China;Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 210028, Nanjing, China;Jiangsu Province Academy of Traditional Chinese Medicine, 210028, Nanjing, China;

关键词: Dissolving microneedles;    Melanoma;    Cannabidiol;    Effervescent;    Tumor microenvironment;    Ca influx;   

DOI  :  10.1186/s40824-023-00390-x

 received in 2023-02-02, accepted in 2023-05-07,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundConventional 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.MethodsIn 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).ResultsUpon 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.ConclusionsThis study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

40517_2023_256_Article_IEq109.gif

40517_2023_256_Article_IEq102.gif

Fig. 1

Fig. 1

Fig. 3

40517_2023_256_Article_IEq38.gif