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绕过P-糖蛋白药物外排机制:在耐药性精神分裂症治疗中的可能应用。

Bypassing P-Glycoprotein Drug Efflux Mechanisms: Possible Applications in Pharmacoresistant Schizophrenia Therapy.

作者信息

Hoosain Famida G, Choonara Yahya E, Tomar Lomas K, Kumar Pradeep, Tyagi Charu, du Toit Lisa C, Pillay Viness

机构信息

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.

出版信息

Biomed Res Int. 2015;2015:484963. doi: 10.1155/2015/484963. Epub 2015 Sep 27.

Abstract

The efficient noninvasive treatment of neurodegenerative disorders is often constrained by reduced permeation of therapeutic agents into the central nervous system (CNS). A vast majority of bioactive agents do not readily permeate into the brain tissue due to the existence of the blood-brain barrier (BBB) and the associated P-glycoprotein efflux transporter. The overexpression of the MDR1 P-glycoprotein has been related to the occurrence of multidrug resistance in CNS diseases. Various research outputs have focused on overcoming the P-glycoprotein drug efflux transporter, which mainly involve its inhibition or bypassing mechanisms. Studies into neurodegenerative disorders have shown that the P-glycoprotein efflux transporter plays a vital role in the progression of schizophrenia, with a noted increase in P-glycoprotein function among schizophrenic patients, thereby reducing therapeutic outcomes. In this review, we address the hypothesis that methods employed in overcoming P-glycoprotein in cancer and other disease states at the level of the BBB and intestine may be applied to schizophrenia drug delivery system design to improve clinical efficiency of drug therapies. In addition, the current review explores polymers and drug delivery systems capable of P-gp inhibition and modulation.

摘要

神经退行性疾病的有效非侵入性治疗常常受到治疗药物向中枢神经系统(CNS)渗透减少的限制。由于血脑屏障(BBB)和相关的P-糖蛋白外排转运体的存在,绝大多数生物活性剂不易渗透到脑组织中。MDR1 P-糖蛋白的过表达与中枢神经系统疾病中多药耐药的发生有关。各种研究成果都集中在克服P-糖蛋白药物外排转运体上,主要涉及对其抑制或绕过机制。对神经退行性疾病的研究表明,P-糖蛋白外排转运体在精神分裂症的进展中起着至关重要的作用,精神分裂症患者中P-糖蛋白功能显著增加,从而降低了治疗效果。在本综述中,我们探讨了这样一个假设:在血脑屏障和肠道水平克服癌症及其他疾病状态下P-糖蛋白的方法,可应用于精神分裂症药物递送系统设计,以提高药物治疗的临床效率。此外,本综述还探讨了能够抑制和调节P-糖蛋白 的聚合物和药物递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/536e/4600488/7cc7b3ea032d/BMRI2015-484963.001.jpg

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