| Nanoparticles attenuate P-glycoprotein/MDR1 function in A549 human alveolar epithelial cells. | |
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MedLine Citation:
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PMID: 21093586 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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P-glycoprotein/MDR1 (P-gp) is a well-characterised membrane transporter relevant in drug disposition and multi-drug resistance. In this study, we aimed to investigate how far nanoparticulates impair the function of the P-gp transport system and which particle properties govern these interactions. Expression and function of P-gp was confirmed in A549 cell monolayers. Rhodamine 123 (Rh123) release studies were carried out in the presence of known inhibitors of P-gp function (i.e., cyclosporine A and verapamil), under ATP depletion (NaN(3)/DOG) and after acute exposure to nanoparticles (NPs) with different surface modifications, ζ-potentials and sizes (plain, carboxylated, and amine- and sulphate-modified). The cytotoxic potential of NPs on A549 monolayers was evaluated by MTT assay. The effects on P-gp protein level, after incubation with NPs, were investigated by Western blot analysis of A549 cell lysate and supernatant. Cellular retention of Rh123 was significantly (P<0.05) increased in the presence of carboxylated (100nm), amine- and sulphate-modified NPs. A slight, but not significant, decrease in Rh123 release was also observed for plain latex and carboxylated (500nm) NPs. The MTT assay demonstrated that most NPs caused only marginal levels of cytotoxicity (78-88% cell viability); the positively charged amine-NPs, however, were considerably more cytotoxic. Western blot showed that NPs did not cause any cell membrane disruption. Our findings suggest that nanomaterials can attenuate membrane transporter function depending on their size and surface properties and hence might influence the disposition of xenobiotics as well as endogenous substrates. |
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Authors:
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Johanna J Salomon; Carsten Ehrhardt |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-11-18 |
Journal Detail:
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Title: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V Volume: - ISSN: 1873-3441 ISO Abbreviation: - Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-12-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9109778 Medline TA: Eur J Pharm Biopharm Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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