Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells.

Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells. Research Abstract Details 

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Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells. Abstract Text:

Ghazal Mohajer,Eun Seong Lee,You Han Bae,

PURPOSE: The purpose of this work was to demonstrate the advantage of using pH-sensitive polymeric mixed micelles (PHSM) composed of poly(L: -histidine) (polyHis)/poly(ethylene glycol) (PEG) and poly(L: -lactic acid) (pLLA)/PEG block copolymers with folate conjugation to increase drug retention in wild-type and MDR tumor cells. MATERIALS AND METHODS: Both wild-type and multidrug resistant (MDR) human breast adenocarcinoma (MCF-7) cell lines were used to investigate the accumulation and elimination of doxorubicin (DOX), PHSM with folate (PHSM/f), and pH-insensitive micelles composed of pLLA/PEG block copolymer with folate (PHIM/f). RESULTS: Cells treated with PHSM/f showed decelerated elimination kinetics compared to cells treated with PHIM/f. MDR cells treated with drug-containing PHSM/f for 30 min retained 80% of doxorubicin (DOX) even after incubation for 24 h in the absence of drug. On the other hand, cells treated with drug-containing PHIM/f retained only 40% of DOX within the same period of time. Flow cytometry and confocal microscopy confirmed these results. CONCLUSIONS: Cellular entry of the micelles occurred via receptor-mediated endocytosis using folate receptors. The pH-induced destabilization of PHSM/f led to rapid distribution of drug and polymer throughout the cells, most likely due to polyHis-mediated endosomal disruption. This reduced the likelihood of drug efflux via exocytosis from resistant tumor cells.

Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells. Publishing Authors By Initials

G Mohajer,ES Lee,YH Bae,

For similar macromolecular substances: polymers research abstracts see: macromolecular substances: polymers research

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Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Pharmaceutical research

VOLUME: 24

Page Numbers: 1618-27

Journal Abbreviation: Pharm. Res.

ISSN: 0724-8741

DAY: 24

MONTH: 03

YEAR: 2007

Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8406521

Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells. Keywords Mesh Terms:

KEYWORDS: Polymers

MESH TERMS: pharmacokinetics

Chemical & Substance for Abstract: Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells. Information

Substance Name: Fluorescein-5-isothiocyanate

Registry Number: 3326-32-7

Grant and Affiliation Information for Enhanced intercellular retention activity of novel pH-sensitive polymeric micelles in wild and multidrug resistant MCF-7 cells.

AFFILIATION: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 315, Salt Lake City, UT 84108, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA101850

ACRONYM: CA

MEDLINETA: Pharm Res

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