title: Pluronics and MDR reversal: an update.
abstract: Multidrug resistance (MDR) remains one of the biggest obstacles for effective cancer therapy. Currently there are only few methods that are available clinically that are used to bypass MDR with very limited success. In this review we describe how MDR can be overcome by a simple yet effective approach of using amphiphilic block copolymers. Triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), arranged in a triblock structure PEO-PPO-PEO, Pluronics or "poloxamers", raised a considerable interest in the drug delivery field. Previous studies demonstrated that Pluronics sensitize MDR cancer cells resulting in increased cytotoxic activity of Dox, paclitaxel, and other drugs by 2-3 orders of magnitude. Pluronics can also prevent the development of MDR in vitro and in vivo. Additionally, promising results of clinical studies of Dox/Pluronic formulation reinforced the need to ascertain a thorough understanding of Pluronic effects in tumors. These effects are extremely comprehensive and appear on the level of plasma membranes, mitochondria, and regulation of gene expression selectively in MDR cancer cells. Moreover, it has been demonstrated recently that Pluronics can effectively deplete tumorigenic intrinsically drug-resistant cancer stem cells (CSC). Interestingly, sensitization of MDR and inhibition of drug efflux transporters is not specific or selective to Pluronics. Other amphiphilic polymers have shown similar activities in various experimental models. This review summarizes recent advances of understanding the Pluronic effects in sensitization and prevention of MDR.
authors.affiliation: Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-7362, United States.
authors.forename: Daria Y
authors.initials: DY
authors.lastname: Alakhova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008055:Lipids / Q000737:chemistry; D021962:Membrane Microdomains / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000166:cytology; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008055:Lipids; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D020442:Poloxamer; D011092:Polyethylene Glycols