High Throughput Synthesis of Micellar Nanocomposites via Liquid-Liquid Electrospray
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2016-02
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Abstract
Purpose of the study: The primary objective of this study is to develop a novel synthesis route for micellar nanocomposites, or micelles, via Liquid-Liquid Electrospray (LLE) in a surfactant free environment. The proposed work will establish a semi-continuous platform to generate high quality nanocomposites for a number of biological applications, including bio-imaging and drug delivery. Multimodal nanocomposites that integrate two or more types of nanoparticles have gained significant attention in the biomedical science and engineering.1-6 More specifically, micelles are polymeric colloids comprises with amphiphilic block copolymers; the presence of both hydrophobic and hydrophilic regions promotes the self-assembly of polymer chains to form a hydrophobic core surrounded by a hydrophilic corona in an aqueous environment. Most applications utilize this unique structural characteristic by loading hydrophobic molecules and/or nanoparticles at the core.7 Standard synthesis techniques (i.e. dialysis, sonication, film hydration) include emulsion based methods8,9, encapsulation during nucleation10,11, and self-assembly12-14. Among these techniques, self-assembly produces the most monodisperse products because the process is thermodynamically driven, minimizing the effect of having a wide range of emulsion droplet size. Interfacial instability (IS) developed by Hayward utilizes the self-assembly of block copolymers to generate micelles. In IS, an organic solvent comprises with block copolymer chains and hydrophobic nanoparticles and/or drug molecules are emulsified in an aqueous solvent.15 As the emulsion droplets undergo the sudden reduction in surface tension due to the hydrophilic block moving toward the organic/aqueous interface, smaller droplets get ejected.15,16 This process repeats itself until the critical concentration of materials is reached to promote self-assembly of nanocomposites. However, these methods are limited to a small scale production due to both energy and material transfer limitations in emulsion formation. As a result, it is desired to establish a scalable synthesis route with an ability to consistently make emulsion droplets. In order to accomplish this goal, electrospray techniques can be employed to atomize organic droplets; by incorporating electrospray, the organic solvent can be dispersed into fine droplets semi-continuously. Furthermore, unlike the conventional electrospray (i.e. aerosol), the spray can be done inside of an aqueous environment (Liquid-in-Liquid), enabling the emulsification without the surfactant that eliminates the downstream purification steps for biological applications. Research method: Liquid-Liquid Electrospray, or LLE, utilizes a stainless steel nozzle that processes organic solvent with micelle constituents. The nozzle is surrounded by a ceramic insulator and placed inside of an aqueous environment (i.e. ultrapure water). In addition to the insulated nozzle, a grounded electrode is placed inside of the aqueous medium. High voltage is applied at the top of the nozzle using a high-voltage power supply, which generates an electric field between the nozzle tip and the grounded electrode inside of the aqueous medium18-20. As the organic solvent is processes through the nozzle, the presence of electric field results in electrohydrodynamic atomization (EHDA)17-20, dispersing the organic solvent into emulsion droplets. These droplets then undergo IS, generating micelles via self-assembly. Overall, this method incorporates both top-down (electrospray) and bottom-up (self-assembly) techniques to produce high quality micelles. Findings: LLE has successfully synthesized nanocomposites encapsulating quantum dots (QDs), superparamagnetic iron oxide nanoparticles (SPIONs), and drug molecules. Size and morphology of nanocomposite were analyzed. Molar ratio of nanoparticles to polymer present in organic phase was found to be the important parameter in tuning the morphology of nanocomposites; by tuning this ratio, fairly monodispersed nanocomposites were obtained. In addition, this study provided valuable insights on the role of surfactants; the absence of surfactant seems to have significant effect on the stability of nanocomposites even after the completion of thermodynamically stable micelle structure. Implication: This study has successfully demonstrated the surfactant free nanocomposite synthesis method at significantly higher throughput in comparison to standard methods. Nanocomposites produced via LLE have been characterized and their functionalities for biological applications (i.e. bio-imaging) have been studied by labeling breast cancer cells with fluorescent QDs. References 1. R. Bakalova, Z. Zhelev, I. Aoki, H. Ohba, Y. Imai, and I. Kanno, Silica-shelled single quantum dot micelles as imaging probes with dual or multimodality. Analytical Chemistry, 2006. 78(16): p. 5925-32. 2. M.F. Kircher, U. Mahmood, R.S. King, R. Weissleder, and L. Josephson, A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Research, 2003. 63(23): p. 8122-5. 3. W.J. Mulder, A.W. Griffioen, G.J. Strijkers, D.P. Cormode, K. Nicolay, and Z.A. Fayad, Magnetic and fluorescent nanoparticles for multimodality imaging. Nanomedicine, 2007. 2(3): p. 307-24. 4. P. Prasad, Emerging Opportunities at the Interface of Photonics, Nanotechnology and Biotechnology. Molecular Crystals and Liquid Crystals, 2006. 446: p. 1-10. 5. P. Sharma, S. Brown, G. Walter, S. Santra, and B. Moudgil, Nanoparticles for bioimaging. Advances in Colloid and Interface Science, 2006. 123-126: p. 471-85. 6. S. Wang, B.R. Jarrett, S.M. Kauzlarich, and A.Y. Louie, Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging. Journal of the American Chemical Society, 2007. 129(13): p. 3848-3856. 7. K. Letchford, & H. Burt. A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. European journal of pharmaceutics and biopharmaceutics, 2007. 65(3): p. 259-269. 8. C.X. Song, V. Labhasetwar, H. Murphy, X. Qu, W.R. Humphrey, R.J. Shebuski, and R.J. Levy, Formulation and characterization of biodegradable nanoparticles for intravascular local drug delivery. Journal of Controlled Release, 1997. 43(2-3): p. 197-212. 9. C.J. Dorcena, K.M. Olesik, O.G. Wetta, and J.O. Winter, Characterization and Toxicity of Carbon Dot-Poly(lactic-co-glycolic acid) Nanocomposites for Biomedical Imaging. Nano Life, 2013. 3(1): p. 1340002. 10. N. Insin, J.B. Tracy, H. Lee, J.P. Zimmer, R.M. Westervelt, and M.G. Bawendi, Incorporation of Iron Oxide Nanoparticles and Quantum Dots into Silica Microspheres. ACS Nano, 2008. 2(2): p. 197-202. 11. V. Salgueirino-Maceira, M.A. Correa-Duarte, M. Spasova, L.M. Liz-Marzan, and M. Farle, Composite silica spheres with magnetic and luminescent functionalities. Advanced Functional Materials, 2006. 16(4): p. 509-514. 12. J.H. Park, G. von Maltzahn, E. Ruoslahti, S.N. Bhatia, and M.J. Sailor, Micellar hybrid nanoparticles for simultaneous magnetofluorescent imaging and drug delivery. Angewandte Chemie International Edition-English, 2008. 47(38): p. 7284-8. 13. G. Ruan, G. Vieira, T. Henighan, A.R. Chen, D. Thakur, R. Sooryakumar, and J.O. Winter, Simultaneous Magnetic Manipulation and Fluorescent Tracking of Multiple Individual Hybrid Nanostructures. Nano Letters, 2010. 10(6): p. 2220-2224. 14. J. Bae, J. Lawrence, C. Miesch, A. Ribbe, W.K. Li, T. Emrick, J.T. Zhu, and R.C. Hayward, Multifunctional Nanoparticle-Loaded Spherical and Wormlike Micelles Formed by Interfacial Instabilities. Advanced Materials, 2012. 24(20): p. 2735-2741. 15. J. Zhu and R.C. Hayward, Spontaneous generation of amphiphilic block copolymer micelles with multiple morphologies through interfacial instabilities. Journal of the American Chemical Society, 2008. 130(23): p. 7496-7502. 16. R. Granek, R.C. Ball, and M.E. Cates, Dynamics of Spontaneous Emulsification. Journal De Physique, 1993. 3(6): p. 829-849. 17. J.R. Melcher, G.I. Taylor, Electrohydrodynamics: a review of the role of interfacial shear stresses, Annual Review of Fluid Mechanics, 1969. 1(1): p. 111 146. 18. M. Sato, M. Saito, and T. Hatori, Emulsification and size control of insulating and/or viscous liquids in liquid-liquid systems by electrostatic dispersion. Journal of colloid and interface science, 1993. 156(2): p. 504-507. 19. M. Sato, I. Kuroiwa, T. Ohshima, and K. Urashima, Production of nano-silica particles in liquid-liquid system by pulsed voltage application. Dielectrics and Electrical Insulation, IEEE Transactions, 2009. 16(2): p. 320-324. 20. M. Sato, I. Kuroiwa, T. Ohshima, and K. 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Description
Engineering: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
Keywords
Micellar Nanocomposites, Liquid-Liquid Electrospray, Nanocomposite synthesis, Electrohydrodynamic Atomization