在癌症治疗中利用维生素 E-TPGS 纳米系统提高多柔比星疗效

IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Journal of Drug Delivery Science and Technology Pub Date : 2024-10-11 DOI:10.1016/j.jddst.2024.106286
Mohd Shoab Ali , Amirhossein Sahebkar , Garima Gupta , Zia Ul-Sabah , Shadma Wahab , Prashant Kesharwani
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摘要

多柔比星是一种常用的化疗药物,但由于肿瘤细胞产生抗药性而造成了巨大的障碍。抗药性机制包括 P-gp 等外排泵的上调、药物代谢的改善以及凋亡的逃避。P-gp 是一种重要的膜结合外排泵,参与癌细胞的多药耐药性。它能主动将许多药物(包括多柔比星等化疗药物)移出细胞,从而降低这些药物的细胞内浓度和效率。MDR1 基因编码这种蛋白质,它在肝脏、肾脏、肠道等多种器官以及许多癌症中都高度表达。抑制 P-gp 活性是对抗耐药性和提高化疗效果的关键方法。因此,人们正在研究新的方法,例如在治疗配方中添加 TPGS(d-α-生育酚聚乙二醇 1000琥珀酸酯),它可以阻断外排泵,提高药物的溶解度和生物利用度。TPGS 是一种水溶性维生素 E 衍生物,具有良好的给药增强功能,由于其两亲性,它可以作为一种表面活性剂,提高溶解性差的药物的溶解度和生物利用度。TPGS 的另一个众所周知的特性是它能够抑制 P-糖蛋白(P-gp),从而使癌细胞能够承受药物并克服药物外流。正因为如此,TPGS 可提高多柔比星等化疗药物的疗效,是配制此类药物的有效成分。本综述文章讨论了 TPGS 在克服多柔比星耐药性方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Enhancing doxorubicin efficacy with vitamin E-TPGS nanosystems in cancer therapy
Doxorubicin, a commonly used chemotherapeutic medication, poses substantial hurdles due to the development of resistance in tumor cells. Resistance mechanisms include up-regulation of efflux pumps such as P-gp, improved drug metabolism, and evasion of apoptosis. P-gp is an important membrane-bound efflux pump involved in multidrug resistance in cancer cells. It decreases the intracellular concentration and efficiency of many medicines, including chemotherapeutics like doxorubicin, by actively moving them out of cells. The MDR1 gene encodes this protein, which is highly expressed in a variety of organs, including the liver, kidney, and intestines, as well as many cancers. Inhibiting P-gp activity is a critical method for combating drug resistance and improving chemotherapeutic effectiveness. Due to this, novel approaches are being investigated, such as adding TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) to therapeutic formulations, which can block efflux pumps and improve drug solubility and bioavailability. TPGS is a water-soluble vitamin E derivative that functions well as an enhancer of drug delivery and because of its amphiphilic nature, it can function as a surfactant which enhances the solubility and bioavailability of poorly soluble medications. Another well-known property of TPGS is its capacity to inhibit P-glycoprotein (P-gp), which allows cancer cells to withstand drugs and overcome drug efflux. Because of this, TPGS is a useful ingredient in the formulation of chemotherapy drugs like doxorubicin by improving their therapeutic effectiveness. The potential of TPGS in overcoming the resistance of doxorubicin was discussed in this review article.
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来源期刊
CiteScore
8.00
自引率
8.00%
发文量
879
审稿时长
94 days
期刊介绍: The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.
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