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用于辅酶Q10经皮给药的醇质体:从设计到3D皮肤组织评估

Ethosomes for Coenzyme Q10 Cutaneous Administration: From Design to 3D Skin Tissue Evaluation.

作者信息

Sguizzato Maddalena, Mariani Paolo, Spinozzi Francesco, Benedusi Mascia, Cervellati Franco, Cortesi Rita, Drechsler Markus, Prieux Roxane, Valacchi Giuseppe, Esposito Elisabetta

机构信息

Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy.

Department of Life and Environmental Sciences, Polytechnic University of Marche, I-60131 Ancona, Italy.

出版信息

Antioxidants (Basel). 2020 Jun 3;9(6):485. doi: 10.3390/antiox9060485.

Abstract

Ethosome represents a smart transdermal vehicle suitable for solubilization and cutaneous application of drugs. Coenzyme Q10 is an endogenous antioxidant whose supplementation can counteract many cutaneous disorders and pathologies. In this respect, the present study describes the production, characterization, and cutaneous protection of phosphatidylcholine based ethosomes as percutaneous delivery systems for coenzyme Q10. CoQ10 entrapment capacity in ethosomes was almost 100%, vesicles showed the typical 'fingerprint' structure, while mean diameters were around 270 nm, undergoing an 8% increase after 3 months from production. An ex-vivo study, conducted by transmission electron microscopy, could detect the uptake of ethosomes in human skin fibroblasts and the passage of the vesicles through 3D reconstituted human epidermis. Immunofluorescence analyses were carried on both on fibroblasts and 3D reconstituted human epidermis treated with ethosomes in the presence of HO as oxidative stress challenger, evaluating 4-hydroxynonenal protein adducts which is as a reliable biomarker for oxidative damage. Notably, the pretreatment with CoQ10 loaded in ethosomes exerted a consistent protective effect against oxidative stress, in both models, fibroblasts and in reconstituted human epidermis respectively.

摘要

乙醇脂质体是一种适用于药物增溶和经皮给药的智能透皮载体。辅酶Q10是一种内源性抗氧化剂,补充它可以对抗多种皮肤疾病和病变。在这方面,本研究描述了基于磷脂酰胆碱的乙醇脂质体作为辅酶Q10经皮给药系统的制备、表征和皮肤保护作用。辅酶Q10在乙醇脂质体中的包封率几乎达到100%,囊泡呈现典型的“指纹”结构,平均直径约为270nm,生产3个月后直径增加了8%。通过透射电子显微镜进行的体外研究能够检测到乙醇脂质体被人皮肤成纤维细胞摄取以及囊泡穿过三维重组人表皮的情况。在以HO作为氧化应激激发剂的情况下,对用乙醇脂质体处理的成纤维细胞和三维重组人表皮进行免疫荧光分析,评估4-羟基壬烯醛蛋白加合物,其作为氧化损伤的可靠生物标志物。值得注意的是,在成纤维细胞和重组人表皮这两种模型中,用负载辅酶Q10的乙醇脂质体进行预处理均对氧化应激产生了一致的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c16/7346166/c92438b7c06a/antioxidants-09-00485-g001.jpg

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