Nanoparticle-Formulated Curcumin Prevents Posttherapeutic Disease Reactivation and Reinfection with Mycobacterium tuberculosis following Isoniazid Therapy.
Nanoparticle-Formulated Curcumin Prevents Posttherapeutic Disease Reactivation and Reinfection with Mycobacterium tuberculosis following Isoniazid Therapy.
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DOI：
10.3389/fimmu.2017.00739
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发表时间：
2017
影响因子：
7.3
通讯作者：
Das G
中科院分区：
文献类型：
--
作者：
Tousif S;Singh DK;Mukherjee S;Ahmad S;Arya R;Nanda R;Ranganathan A;Bhattacharyya M;Van Kaer L;Kar SK;Das G
姜黄素是姜黄的生物活性成分，也被称为“印度黄金”，对几种慢性炎症和感染性疾病具有治疗功效。尽管姜黄素被认为是一种与无数报道的益处有关的神奇药物，但由于其肠道吸收差、代谢快和全身消除快，姜黄素的转化潜力受到其全身生物利用度低的限制。因此，这种化合物的转化潜力受到生物利用度问题的挑战，一些实验室正在努力提高其生物利用度。我们开发了一种简单的一步法来产生尺寸约为200 nm的姜黄素纳米颗粒，其在小鼠中的生物利用度比常规姜黄素提高了五倍。姜黄素纳米粒在小鼠治疗期间显著降低抗结核抗生素诱导的肝毒性。最有趣的是，纳米颗粒配制的姜黄素沿着抗结核抗生素的共同治疗显著降低了疾病再激活和再感染的风险，这是直接观察治疗短期采用的当前抗生素治疗的主要不足。此外，纳米颗粒配制的姜黄素显着减少了抗生素治疗获得无菌免疫所需的时间，从而降低了产生生物体耐药性变体的可能性。因此，具有增强的生物利用度的纳米制剂姜黄素的辅助治疗可能有益于治疗结核病和可能的其他疾病。
Curcumin, the bioactive component of turmeric also known as “Indian Yellow Gold,” exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. Even though considered as a wonder drug pertaining to a myriad of reported benefits, the translational potential of curcumin is limited by its low systemic bioavailability due to its poor intestinal absorption, rapid metabolism, and rapid systemic elimination. Therefore, the translational potential of this compound is specifically challenged by bioavailability issues, and several laboratories are making efforts to improve its bioavailability. We developed a simple one-step process to generate curcumin nanoparticles of ~200 nm in size, which yielded a fivefold enhanced bioavailability in mice over regular curcumin. Curcumin nanoparticles drastically reduced hepatotoxicity induced by antitubercular antibiotics during treatment in mice. Most interestingly, co-treatment of nanoparticle-formulated curcumin along with antitubercular antibiotics dramatically reduced the risk for disease reactivation and reinfection, which is the major shortfall of current antibiotic treatment adopted by Directly Observed Treatment Short-course. Furthermore, nanoparticle-formulated curcumin significantly reduced the time needed for antibiotic therapy to obtain sterile immunity, thereby reducing the possibility of generating drug-resistant variants of the organisms. Therefore, adjunct therapy of nano-formulated curcumin with enhanced bioavailability may be beneficial to treatment of tuberculosis and possibly other diseases.