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Reports Outline Multidrug Resistance Study Results from University Health Network (Synergistic Nanoparticulate Drug Combination Overcomes Multidrug...

September 10, 2014



Reports Outline Multidrug Resistance Study Results from University Health Network (Synergistic Nanoparticulate Drug Combination Overcomes Multidrug Resistance, Increases Efficacy, and Reduces Cardiotoxicity in a Nonimmunocompromised Breast ...)

By a News Reporter-Staff News Editor at Biotech Week -- Researchers detail new data in Drug Resistance. According to news reporting originating in Toronto, Canada, by NewsRx journalists, research stated, "Anthracyclines, commonly employed for cancer chemotherapy, suffer from dose-limiting cardiotoxicity and poor efficacy due to multidrug resistance (MDR). We previously demonstrated that simultaneous delivery of the synergistic drugs doxorubicin (DOX) and mitomycin C (MMC) by polymer lipid hybrid nanoparticles (PLN) circumvented MDR, increased efficacy, and reduced cardiotoxicity in immuncompromised mice superior to poly(ethylene glycol)-coated (PEGylated) lipososmal DOX (PLD)."

The news reporters obtained a quote from the research from University Health Network, "Herein it is shown that the DOX-MMC combination was also synergistic in MDR EMT6/AR1 murine breast cancer cells and that their nanoparticle formulations were able to overcome the MDR phenotype. In contrast PLD exhibited little or no effect on the MDR cells. For the first time, these differences in in vitro efficacy are shown to be strongly correlated with cellular uptake and intracellular distribution of DOX brought about by DOX formulations (e.g., free solution, PLN vs PLD). To take into consideration the role of an intact immune system and tumor stroma in the response of host and tumor to chemotherapy, use was made of nonimmunocomprised mouse models to study the dose tolerance, cardiotoxicity, and efficacy of DOX-MMC coloaded PLN (DMsPLN) compared to PLD. DMsPLN treatment at SO mg/m2 DOX and 17 mg/m2 of MMC singly or once every 4 days for 4 cycles were well tolerated by the mice without elevated systemic toxicity blood markers or myocardial damage. In contrast, PLD was limited to a single treatment due to significant total weight loss. The DMsPLN treatment delayed tumor growth up to 31296 and 28% in EMT6/WT and EMT6/AR1 models, respectively."

According to the news reporters, the research concluded: "This work supports the translational value of DMsPLN for the aggressive management of either na ve or anthracycline-resistant tumors."

For more information on this research see: Synergistic Nanoparticulate Drug Combination Overcomes Multidrug Resistance, Increases Efficacy, and Reduces Cardiotoxicity in a Nonimmunocompromised Breast Tumor Model. Molecular Pharmaceutics, 2014;11(8):2659-2674. Molecular Pharmaceutics can be contacted at: Amer Chemical Soc, 1155 16TH St, NW, Washington, DC 20036, USA. (American Chemical Society - www.acs.org; Molecular Pharmaceutics - www.pubs.acs.org/journal/mpohbp)

Our news correspondents report that additional information may be obtained by contacting A.J. Shuhendler, Univ Hlth Network, Princess Margaret Canc Center, Toronto, ON M5T 2M9, Canada. Additional authors for this research include P. Prasad, R.X. Zhang, M.A. Amini, M. Sun, P.P. Liu, R.G. Bristow, A.M. Rauth and X.Y. Wu (see also Drug Resistance).

Keywords for this news article include: Toronto, Ontario, Canada, North and Central America, Drug Resistance, Multidrug Resistance, Therapy

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Biotech Week


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