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甘草查尔酮A-多糖自组装纳米粒在健康和二硝基氯苯诱导的Balb/c小鼠特应性皮炎模型中的渗透差异

Differences in the permeation of Licoricchalcone A-polysaccharide self-assembled nanoparticles on healthy and DNCB-induced atopic dermatitis in Balb/c mice.

作者信息

Chen Li, Xue Yuye, Wang Fang, Song Rui, Zhu YuWen, Ning Jiantao, Zha Wenting, Deng Xiang, Hang Lingyu, Gu Weijie, Yuan Hailong

机构信息

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu 611137, Sichuan, China; Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China.

Department of Pharmacy, Air Force Medical Center, PLA, Air Force Medical University, Beijing 100142, China.

出版信息

Int J Biol Macromol. 2024 Dec;282(Pt 3):136984. doi: 10.1016/j.ijbiomac.2024.136984. Epub 2024 Oct 28.

Abstract

Nanoformulation have been widely used in skin and transdermal drug delivery. However, the differences in integral nanoparticles absorption in healthy and diseased skin have not yet fully analyzed. The present study attempted to explore the percutaneous absorption of drugs via lesional skin by using atopic dermatitis (AD) as a model, dinitrochlorobenzene (DNCB) induced AD-like skin. In here, the small molecules of insoluble Licoricchalcone A (LA) and macromolecules glycyrrhizin polysaccharide were used to prepare LA-polysaccharide self-assembled nanoparticles (GPA-SANs) by micro-precipitation. An environment-responsive dye, P4, was loaded into SAN to track the transdermal translocation of the nanoparticles, while the drug marked with coumarin 6 (C6). Compared to healthy skin, the permeability of GPA-SANs on AD-like skin is stronger, which may be due to damage to the stratum corneum of the AD-like skin and increased intercellular spaces, resulting in an increased permeability coefficient. Therefore, the storage of nanoparticles and their diffusion at the lesion site also increased accordingly. CLSM shown that the fluorescence of P4 and C6 is observed to concentrate around the hair follicles and disseminate in the surrounding area in both AD-affected and healthy skin. It can be clearly seen that fluorescence signal of C6 in the intercellular spaces of the dermis and epidermis of AD-like skin, indicating that nano-drug on the disease skin can penetrate through the intercellular pathway to achieve therapeutic. The focus of the present study is to assess the permeability of healthy and disease skin, discuss their characteristics and discrepancy, aiming to provide a reference for the further study of nano-formulations in transdermal delivery.

摘要

纳米制剂已广泛应用于皮肤和透皮给药。然而,健康皮肤和患病皮肤中完整纳米颗粒吸收的差异尚未得到充分分析。本研究试图以特应性皮炎(AD)为模型,利用二硝基氯苯(DNCB)诱导的类AD皮肤,探索药物经皮损皮肤的经皮吸收。在此,使用不溶性甘草查尔酮A(LA)的小分子和大分子甘草酸多糖,通过微沉淀法制备LA-多糖自组装纳米颗粒(GPA-SANs)。将一种环境响应性染料P4载入SAN中,以追踪纳米颗粒的透皮转运,同时将标记有香豆素6(C6)的药物载入其中。与健康皮肤相比,GPA-SANs在类AD皮肤上的渗透性更强,这可能是由于类AD皮肤角质层受损以及细胞间隙增加,导致渗透系数增加。因此,纳米颗粒在病变部位的储存及其扩散也相应增加。共聚焦激光扫描显微镜(CLSM)显示,在受AD影响的皮肤和健康皮肤中,均观察到P4和C6的荧光集中在毛囊周围并在周围区域扩散。可以清楚地看到,类AD皮肤真皮和表皮细胞间隙中有C6的荧光信号,表明疾病皮肤上的纳米药物可以通过细胞间途径渗透以实现治疗。本研究的重点是评估健康皮肤和患病皮肤的渗透性,讨论它们的特性和差异,旨在为纳米制剂在透皮给药方面的进一步研究提供参考。

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