化学渗透促进剂对米诺地尔体外经大鼠皮肤渗透的影响:机制研究

Q4 Pharmacology, Toxicology and Pharmaceutics

Iranian Journal of Pharmaceutical Sciences Pub Date : 2018-01-01 DOI:10.22034/IJPS.2018.32053

Eskandar Mmoghimipour, A. Salimi, Ali Talebpour Jahromi

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引用次数: 4

摘要

摘要:米诺地尔是一种嘧啶衍生物(2,4 -二氨基-6-哌啶嘧啶-3-氧化物)，是目前唯一一种被证实有效的治疗皮肤渗透性和生物利用度较低的雄激素性脱发的药物。本研究的主要目的是探讨一些渗透促进剂对米诺地尔体外皮肤渗透性的影响。在制备的Franz扩散池中对经尿素、桉树油和薄荷醇等渗透促进剂预处理的大鼠皮肤进行米诺地尔渗透实验，并与水合大鼠皮肤作对照。采用傅里叶变换红外光谱(FTIR)，通过比较角蛋白(Amide II)吸光度的不对称(Asy)和对称(Sym) C- h拉伸、C=O拉伸、C=O拉伸(Amide I)和C- n拉伸的峰位变化及其强度，研究了渗透增强剂的渗透增强机理。并通过差示扫描量热法(DSC)比较平均转变温度(Tm)和它们的焓(∆H)。用桉树油、薄荷醇和尿素等化学增强剂对米诺地尔在大鼠皮肤中的渗透性参数进行了评价。皮肤对米诺地尔的全皮肤渗透性有屏障，扩散到皮肤是药物通量的限速步骤。尿素、桉树油和薄荷醇是最有效的增强剂，其通量分别是水皮肤的1.86倍、2.16倍和1.75倍，扩散系数分别是水皮肤的3.25倍、1.34倍和2.16倍。FTIR和DSC结果显示，渗透增强剂对皮肤SC层的脂质流态化、提取、脂质结构破坏和蛋白质不可逆变性。

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Influence of Chemical Permeation Enhancers on the in vitro Skin Permeation of Minoxidil through Excised Rat Skin: A Mechanistic Study

Abstract: Minoxidil, a pyrimidine derivative (2, 4-diamino-6-piperidinopyrimidine-3-oxide) is the only topical medical treatment with proven efficacy for the treatment of Androgenetic alopecia that shown low skin penetration and bioavailability. The main aim of this research was to investigate the effect of some permeation enhancers on the in vitro skin permeability of minoxidil . Minoxidil permeability experiments through rat skin pretreated with some of permeation enhancers namely, Urea, Eucalyptus oil and Menthol were performed in fabricated Franz diffusion cells and compared with hydrated rat skin as control. The permeability parameters evaluated include steady-state flux (Jss), permeability coefficient (Kp) and diffusion coefficient (D). The penetration enhancer’s permeability enhancement mechanisms were investigated by comparing of changes in peak position and their intensities of asymmetric (Asy) and symmetric (Sym) C-H stretching, C=O stretching, C=O stretching (Amide I) and C-N stretching of keratin (Amide II ) absorbance using Fourier transform infrared spectroscopy (FTIR), as well as by comparing mean transition temperature (Tm) and their enthalpies (∆H) using differential scanning calorimetery (DSC). Minoxidil permeability parameters through rat skin, were evaluated with and without chemical enhancers such as Eucalyptus oil, menthol and urea. The skin showed barrier for minoxidil permeability through whole skin and that diffusion into the skin was the rate-limiting step for drug flux. Urea , Eucalyptus oil and Menthol were the most effective enhancers as they increased flux 1.86 ,2.16 and 1.75 times and diffusion coefficient 3.25,1.34 and 2.16 folds in comparison with hydrated skin, respectively. FTIR and DSC results showed lipid fluidization , extraction ,disruption of lipid structure and irreversible denaturation of proteins in the SC layer of skin by permeation enhancers.

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来源期刊

Iranian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

0.50

自引率

0.00%

发文量

期刊介绍： Iranian Journal of Pharmaceutical Sciences (IJPS) is an open access, internationally peer-reviewed journal that seeks to publish research articles in different pharmaceutical sciences subdivisions: pharmacology and toxicology, nanotechnology, pharmaceutics, natural products, biotechnology, pharmaceutical chemistry, clinical pharmacy and other pharmacy related topics. Each issue of the journal contents 16 outstanding research articles in area of pharmaceutical sciences plus an editorial written by the IJPS editors on one of the most up to date advances topics in pharmacy. All articles published by IJPS would be permanently accessible online freely without any subscription charges. Authors of the published articles have granted the right to use and disseminate their article to third parties.