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MAL-associated methyl nicotinate for topical PDT improvement
Journal of Photochemistry and Photobiology B: Biology ( IF 3.9 ) Pub Date : 2020-11-02 , DOI: 10.1016/j.jphotobiol.2020.112071
Mirian Denise Stringasci , Heloísa Ciol , Renan Arnon Romano , Hilde Harb Buzza , Ilaiáli Souza Leite , Natalia Mayumi Inada , Vanderlei Salvador Bagnato

Photosensitization of all tissue in sufficient quantity to generate damage is one of the limiting factors for Photodynamic Therapy (PDT) efficiency. Methyl nicotinate (MN) is a thermogenic and vasodilating substance that facilitates the topical tissue penetration of some compounds. The topical MAL (methyl aminolevulinate) PDT is commonly used as a precursor of protoporphyrin IX (PpIX). This study investigates the safety of topical use in NM, as well as its ability to improve the efficiency of topical PDT. For this, we investigate the cytotoxicity of MN, as well as its actions in increasing cellular metabolism and vasodilation. Besides, its ability to optimize the formation of PpIX in the tissue when associated with MAL cream was investigated, besides assessing the severity of necrosis obtained by treatments. The cytotoxicity of MN was tested for concentrations of 0, 0.1, 0.25, 0.5, 0.75 and 1% in cell culture. For the concentration of 0.5%, the cellular metabolism was evaluated using confocal microscopy to calculate the redox rate. In the Chorioallantoic Membrane Model, vasodilation was evaluated for concentrations of 0.5 and 1% MN during 1 h of incubation. In the animal model, the healthy skin of Wistar rat was used to evaluate the production of PpIX in the tissue and the degree of necrosis obtained by Photodynamic therapy when using NM associated with methyl aminolevulinate. It was observed the non-cytotoxicity in vitro of MN in the concentration used (0.5%) and its ability to increase cellular metabolism. In a chorioallantoic model, the MN vasodilation power was demonstrated for different caliber of vessels. In vivo studies are showing that the incorporation of MN in the MAL cream increases the amount of PpIX produced in the tissue causing a higher effect on the epidermis after PDT. This improvement of the protocol may make the procedure more effective both in the destruction of tumor tissue and in the treatment of deeper cells decreasing possible recurrence, in addition to allowing improvements in the protocol, such as reducing the cream's incubation time.



中文翻译:

MAL相关烟酸甲酯可改善局部PDT

所有组织的光敏化足以产生损伤是光动力疗法(PDT)效率的限制因素之一。烟酸甲酯(MN)是一种热源性和血管舒张性物质,可促进某些化合物的局部组织渗透。局部用MAL(氨基乙酰丙酸甲酯)PDT通常用作原卟啉IX(PpIX)的前体。这项研究调查了局部使用在NM中的安全性,以及其提高局部PDT效率的能力。为此,我们研究了MN的细胞毒性,以及其在增加细胞代谢和血管舒张中的作用。此外,除了评估通过治疗获得的坏死的严重程度外,还研究了其与MAL乳霜结合时优化组织中PpIX形成的能力。在细胞培养物中,对于浓度为0、0.1、0.25、0.5、0.75和1%的MN,测试其细胞毒性。对于0.5%的浓度,使用共聚焦显微镜评估细胞代谢以计算氧化还原速率。在绒毛膜尿囊膜模型中,在孵育1小时期间评估了血管舒张的MN浓度为0.5和1%。在动物模型中,将Wistar大鼠的健康皮肤用于评估组织中PpIX的产生以及使用NM与氨基乙酰丙酸甲酯相关联时通过光动力疗法获得的坏死程度。观察到无细胞毒性 在孵育1小时期间评估了血管舒张的MN浓度为0.5和1%。在动物模型中,将Wistar大鼠的健康皮肤用于评估组织中PpIX的产生以及使用NM与氨基乙酰丙酸甲酯相关联时通过光动力疗法获得的坏死程度。观察到无细胞毒性 在孵育1小时期间评估了血管舒张的MN浓度为0.5和1%。在动物模型中,将Wistar大鼠的健康皮肤用于评估组织中PpIX的产生以及使用NM与氨基乙酰丙酸甲酯相关联时通过光动力疗法获得的坏死程度。观察到无细胞毒性MN在体外的浓度(0.5%)及其增加细胞代谢的能力。在绒毛膜尿囊症模型中,证明了不同口径血管的MN血管舒张能力。体内研究表明,在MAL乳膏中掺入MN会增加组织中产生的PpIX的量,从而在PDT后对表皮产生更高的作用。方案的这种改进可以使该程序在破坏肿瘤组织和治疗更深层的细胞中更有效,从而减少可能的复发,此外还可以改进方案,例如减少乳霜的孵育时间。

更新日期:2020-11-23
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