Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
Drug Discov Today. 2024 Sep;29(9):104108. doi: 10.1016/j.drudis.2024.104108. Epub 2024 Jul 19.
The primary challenge in TB treatment is the emergence of multidrug-resistant TB (MDR-TB). One of the major factors responsible for MDR is the upregulation of efflux pumps. Permeation-glycoprotein (P-gp), an efflux pump, hinders the bioavailability of the administered drugs inside the infected cells. Simultaneously, angiogenesis, the formation of new blood vessels, contributes to drug delivery complexities. TB infection triggers a cascade of events that upregulates the expression of angiogenic factors and P-gp. The combined action of P-gp and angiogenesis foster the emergence of MDR-TB. Understanding these mechanisms is pivotal for developing targeted interventions to overcome MDR in TB. P-gp inhibitors, such as verapamil, and anti-angiogenic drugs, including bevacizumab, have shown improvement in TB drug delivery to granuloma. In this review, we discuss the potential of P-gp inhibitors as an adjunct therapy to shorten TB treatment.
结核治疗的主要挑战是耐多药结核(MDR-TB)的出现。导致 MDR 的一个主要因素是外排泵的上调。外排泵渗透糖蛋白(P-gp)会降低感染细胞内给予药物的生物利用度。同时,血管生成,即新血管的形成,会增加药物输送的复杂性。结核感染会引发一连串事件,上调血管生成因子和 P-gp 的表达。P-gp 和血管生成的共同作用促进了 MDR-TB 的出现。了解这些机制对于开发针对结核 MDR 的靶向干预措施至关重要。P-gp 抑制剂,如维拉帕米,以及抗血管生成药物,如贝伐珠单抗,已显示出在改善结核药物向肉芽肿输送方面的作用。在这篇综述中,我们讨论了 P-gp 抑制剂作为辅助治疗方法来缩短结核治疗时间的潜力。