1.Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy.
Ting WEN ; Yanping FU ; Xiangting YI ; Ying SUN ; Wanchen ZHAO ; Chaonan SHI ; Ziyao CHANG ; Beibei YANG ; Shuling LI ; Chao LU ; Tingting PENG ; Chuanbin WU ; Xin PAN ; Guilan QUAN
Acta Pharmaceutica Sinica B 2025;15(7):3738-3755
Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO2 bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.
2.Inhibitory effects of Huoxue Jiedu decoction on cellapoptosis via down-regulating 8-OhdG in obstructive nephropathy rats
Zheng WANG ; Yi CHANG ; Yunzhao XIONG ; Xuan WANG ; Conghui WANG ; Miao WANG ; Xiangting WANG ; Dongyun SUN ; Lijuan LIANG ; Qingyou XU
Chinese Pharmacological Bulletin 2017;33(9):1324-1329
Aim To observe the effect of eplerenone(EPL) and Chinese decoction on cell apoptosis in obstructive nephropathy rats.Methods Sixty male Wistar rats were randomly divided into sham group, UUO group, EPL group and ZY group(n=15).Except sham group, the rats in the other groups were ligated with unilateral ureteral obstruction(UUO) for renal interstitial fibrosis model.The rats were treated with eplerenone at 100 mg·kg-1·d-1 added to diet in EPL group, and orally 13.7 g·kg-1·d-1 decoction of Chinese medicine in ZY group.The kidneys were harvested on 14th day, the number of renal cell apoptosis were detected by TUNEL, and serum aldosterone and 8-OhdG were detected with radioimmunoassay and ELISA.Caspase-12, caspase-9, Bax and Bcl-2 were examined by immunohistochemistry and Western blot.Results The levels of serum aldosterone, serum and urine 8-OhdG and the number of positive apoptotic cells increased significantly in UUO rats compared with Sham group.The overexpression of caspase-9, caspase-12 and Bax and down-regulated Bcl-2 were obvious in UUO group(P<0.01).The level of 8-OhdG, expression of caspase-9, caspase-12 and Bax were down-regulated, and Bcl-2 expression was up-regulated in eplerenone and Chinese decoction treated rats(P<0.01).Conclusion Eplerenone and Chinese decoction could inhibit cell apoptosis induced by oxidative damage after UUO via caspases and(or) Bax pathway.

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