Generation of toxic degradation products by sonication of Pluronic® dispersants: implications for nanotoxicity testing

Abstract Poloxamers (known by the trade name Pluronic®) are triblock copolymer surfactants that contain two polyethylene glycol blocks and one polypropylene glycol block of various sizes. Poloxamers are widely used as nanoparticle dispersants for nanotoxicity studies wherein nanoparticles are sonicated with a dispersant to prepare suspensions. It is known that poloxamers can be degraded during sonication and that reactive oxygen species contribute to the degradation process. However, the possibility that poloxamer degradation products are toxic to mammalian cells has not been well studied. We report here that aqueous solutions of poloxamer 188 (Pluronic® F-68) and poloxamer 407 (Pluronic® F-127) sonicated in the presence or absence of multi-walled carbon nanotubes (MWNTs) can became highly toxic to cultured cells. Moreover, toxicity correlated with the sonolytic degradation of the polymers. These findings suggest that caution should be used in interpreting the results of nanotoxicity studies where the potential sonolytic degradation of dispersants was not controlled.

[1]  Sonochemistry , 1990, Science.

[2]  S. Koda,et al.  Ultrasonic degradation of water-soluble polymers , 1994 .

[3]  E. A. Neppiras Acoustic cavitation series: part one , 1984 .

[4]  B. Masereel,et al.  Effects of the dispersion methods in Pluronic F108 on the size and the surface composition of MWCNTs and their implications in toxicology assessment , 2011 .

[5]  M. Almgren,et al.  Effect of potassium fluoride on the micellar behavior of Pluronic F-68 in aqueous solution , 1992 .

[6]  G. Madras,et al.  Effect of temperature on the ultrasonic degradation of polyacrylamide and poly(ethylene oxide) , 2004 .

[7]  Kenneth S Suslick,et al.  Inside a collapsing bubble: sonoluminescence and the conditions during cavitation. , 2008, Annual review of physical chemistry.

[8]  C. Mikoryak,et al.  Cytotoxicity screening of single-walled carbon nanotubes: detection and removal of cytotoxic contaminants from carboxylated carbon nanotubes. , 2011, Molecular pharmaceutics.

[9]  Laurie G Hudson,et al.  Role of polyethylene glycol integrity in specific receptor targeting of carbon nanotubes to cancer cells. , 2009, Nano letters.

[10]  Mark R. Wiesner,et al.  Ultrasonic dispersion of nanoparticles for environmental, health and safety assessment – issues and recommendations , 2011, Nanotoxicology.

[11]  Marco Aurélio Zezzi Arruda,et al.  Use of ultrasonic baths for analytical applications: a new approach for optimisation conditions , 2001 .

[12]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[13]  P. Riesz,et al.  Adsorption of surfactants at the gas/solution interface of cavitation bubbles: An ultrasound intensity-independent frequency effect in sonochemistry , 2002 .

[14]  M. Kurfürst Detection and molecular weight determination of polyethylene glycol-modified hirudin by staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. , 1992, Analytical biochemistry.

[15]  Benjamin Chu,et al.  Light-scattering study on the association behavior of triblock polymers of ethylene oxide and propylene oxide in aqueous solution , 1988 .

[16]  R. Arakawa,et al.  Mass spectrometric analysis for high molecular weight synthetic polymers using ultrasonic degradation and the mechanism of degradation. , 2007, Analytical chemistry.

[17]  P. Dario,et al.  Dispersion of Multi‐walled Carbon Nanotubes in Aqueous Pluronic F127 Solutions for Biological Applications , 2009 .

[18]  K. Suslick,et al.  Applications of Ultrasound to Materials Chemistry , 1995 .

[19]  G. Madras,et al.  Effect of initial molecular weight and solvents on the ultrasonic degradation of poly(ethylene oxide) , 2005 .

[20]  R. Arakawa,et al.  Determination of primary bond scissions by mass spectrometric analysis of ultrasonic degradation products of poly(ethylene oxide-block-propylene oxide) copolymers. , 2010, Journal of mass spectrometry : JMS.

[21]  T. A. Hatton,et al.  Micellization of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers in aqueous solutions: Thermodynamics of copolymer association , 1994 .