Delivery of P-glycoprotein substrates using chemosensitizers and nanotechnology for selective and efficient therapeutic outcomes

详细信息	查看全文 | 推荐本文 |

• 作者：Rita Nieto Montesinos^a ; ^{rita.nieto_montesinos@univ-fcomte.fr} ; Arnaud Bé ; duneau^a ; Yann Pellequer^a ; Alf Lamprecht^a ; ^b
• 关键词：P-glycoprotein ; Drug efflux ; P-gp modulators ; Nanocarriers ; Drug delivery strategies
• 刊名：Journal of Controlled Release
• 出版年：2012
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：10 July, 2012
• 卷：161
• 期：1
• 页码：50-61
• 文件大小：508 K

摘要

As a result of its broad substrate specificity and critical localization in excretory and barrier function tissues, P-glycoprotein (P-gp) plays major roles in the pharmacokinetics, safety and efficacy profiles of numerous drugs. P-gp is often responsible for the failure of many chemical treatments against cancer, immunosuppressive, infectious and neurodegenerative diseases. Among the therapeutic approaches to circumvent P-gp function, advances in the design of new chemical P-gp modulators to interact specifically with P-gp have yielded few clinical successful reports. Members of a class of components that were initially developed as surface active agents showed promising results with regard to the modulation of P-gp. These components include surfactants and amphiphilic co-polymers. Alternatively, colloidal systems were developed to facilitate drug uptake in resistant cells. This approach is based on the encapsulation of drugs, which masks them from the biological environment and prevents their transport by P-gp using the surfactants released from the nanocarrier. Likewise, a novel and synergistic strategy is currently being explored and involves nanocarrier-mediated transport and controlled release of both P-gp substrates and P-gp modulators. In this review, we discuss recent results obtained by direct modulation with chemosensitizers and the available nanotechnology to modulate P-gp function. In this manuscript, we also discuss unexplored pathways for future therapies.