Formation and enhanced biocidal activity of water-dispersable organic nanoparticles

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Abstract

Water-insoluble organic compounds are often used in aqueous environments in various pharmaceutical and consumer products. To overcome insolubility, the particles are dispersed in a medium during product formation1, but large particles that are formed may affect product performance and safety. Many techniques have been used to produce nanodispersions—dispersions with nanometre-scale dimensions—that have properties similar to solutions2,3,4. However, making nanodispersions requires complex processing, and it is difficult to achieve stability over long periods1. Here we report a generic method for producing organic nanoparticles with a combination of modified emulsion-templating5 and freeze-drying. The dry powder composites formed using this method are highly porous, stable and form nanodispersions upon simple addition of water. Aqueous nanodispersions of Triclosan (a commercial antimicrobial agent) produced with this approach show greater activity than organic/aqueous solutions of Triclosan.

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Figure 1: Characterization of solid nanocomposites and nanodispersions.
Figure 2: Comparison of conventional surfactant solubilization and nanodispersions of Oil-Red (OR).
Figure 3: Schematic/mechanistic representation of nanoparticle formation during freeze-drying.
Figure 4: Scanning electron microscopy images of freeze-dried atomized powders.
Figure 5: Evaluation of the minimum inhibitory concentration (MIC) of different forms of the antibacterial agent Triclosan.

References

  1. 1

    Abdelwahed, W., Degobert, G., Stainmesse, S. & Fessi, H. Freeze-drying of nanoparticles: Formulation, process and storage considerations. Adv. Drug Deliv. Rev. 58, 1688–1713 (2006).

  2. 2

    Mizoe, T., Ozeki, T. & Okada, H. Preparation of drug nanoparticle-containing microparticles using a 4-fluid nozzle spray drier for oral, pulmonary and injection dosage forms. J. Contr. Rel. 122, 10–15 (2007).

  3. 3

    Texter, J. Precipitation and condensation of organic particles. J. Disp. Sci. Technol. 22, 499–527 (2001).

  4. 4

    Horn, D. & Rieger, J. Organic nanoparticles in the aqueous phase—theory, experiment and use. Angew. Chem. Int. Ed. Engl. 40, 4330–4361 (2001).

  5. 5

    Zhang, H. & Cooper, A. I. Synthesis and applications of emulsion-templated porous materials. Soft Matter 1, 107–113 (2005).

  6. 6

    Royal Society and Royal Academy of Engineering Nanoscience and Nanotechnologies. Nanoscience and Nanotechnologies: Opportunities and Uncertainties, Report (Royal Society and Royal Academy of Engineering Nanoscience and Nanotechnologies, 2004) <http://www.nanotec.org.uk/finalReport.htm>.

  7. 7

    Rabinow, B. E. Nanosuspensions in drug delivery. Nature Rev. Drug Discov. 3, 785–796 (2004).

  8. 8

    Galindo-Rodríguez, S. A. et al. Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles. Eur. J. Pharm. Sci. 25, 357–367 (2005).

  9. 9

    Lee, J. C. et al. Preparation, stability and in vitro performance of vesicles made with diblock copolymers. Biotechnol. Bioeng. 73, 135–145 (2001).

  10. 10

    Sethi, V., Önyüksel, H. & Rubinstein, I. Liposomal vasoactive intestinal peptide. Method. Enzymol. 391, 377–395 (2005).

  11. 11

    Kita-Tokarczyk, K., Grumelard, J., Haefele, T. & Meier, W. Block copolymer vesicles — using concepts from polymer chemistry to mimic biomembranes. Polymer 46, 3540–3563 (2005).

  12. 12

    Cameron, N. R. High internal phase emulsion templating as a route to well-defined porous polymers. Polymer 46, 1439–1449 (2005).

  13. 13

    Dwivedi, A. M. Residual solvent analysis in pharmaceuticals. Pharm. Technol. Eur. 14, 26–28 (2002).

  14. 14

    Gilanyi, T. & Wolfram, E. Interaction of ionic surfactants with polymers in aqueous solution. Coll. Surf. 3, 181–198 (1981).

  15. 15

    Tang, X. & Pikal, M. J. Design of freeze-drying processes for pharmaceuticals: practical advice. Pharm. Res. 21, 191–200 (2004).

  16. 16

    Franks, F. Freeze-drying of bioproducts: putting principles into practice. Eur. J. Pharm. Biopharm. 45, 221–229 (1998).

  17. 17

    Craig, D. Q. M., Royall, P. G., Kett, V. L. & Hopton, M. L. The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze-dried systems. Int. J. Pharm. 179, 179–207 (1999).

  18. 18

    Zhang, H. et al. Aligned two- and three-dimensional structures by directional freezing of polymers and nanoparticles. Nature Mater. 4, 787–793 (2005).

  19. 19

    Yu, Z., Rogers, T. L., Hu, J., Johnston, K. P. & Williams, R. O. Preparation and characterization of microparticles containing peptide produced by a novel process: spray freezing into liquid. Eur. J. Pharm. Biopharm. 54, 221–228 (2002).

  20. 20

    Rogers, T. L. et al. Micronized powders of a poorly water soluble drug produced by a spray-freezing into liquid-emulsion process. Eur. J. Pharm. Biopharm. 55, 161–172 (2003).

  21. 21

    Skrabalak, S. E. & Suslick, K. S. Porous MoS2 synthesized by ultrasonic spray pyrolysis. J. Am. Chem. Soc. 127, 9990–9991 (2005).

  22. 22

    Iskandar, F., Mikrajuddin & Okuyama, K. Controllability of pore size and porosity on self-organized porous silica particles. Nano Lett. 2, 389–392 (2002).

  23. 23

    Suh, W. H. & Suslick, K. S. Magnetic and porous nanospheres from ultrasonic spray pyrolysis. J. Am. Chem. Soc. 127, 12007–12010 (2005).

  24. 24

    DeSimone, J. M. Practical approaches to green solvents. Science 297, 799–803 (2002).

  25. 25

    Cooper, A. I. Porous materials and supercritical fluids. Adv. Mater. 15, 1049–1059 (2003).

  26. 26

    Zhang, H., Long, J. & Cooper, A. I. Aligned porous materials by directional freezing of solutions in liquid CO2 . J. Am. Chem. Soc. 127, 13482–13483 (2005).

  27. 27

    Butler, R., Hopkinson, I. & Cooper, A. I. Synthesis of porous emulsion-templated polymers using high internal phase CO2-in-water emulsions. J. Am. Chem. Soc. 125, 14473–14481 (2003).

  28. 28

    Tan, B. & Cooper, A. I. Functional oligo(vinyl acetate) CO2-philes for solubilization and emulsification. J. Am. Chem. Soc. 127, 8938–8939 (2005).

  29. 29

    Taylor, T. J. et al. Physicochemical factors affecting the rapid bactericidal efficacy of the phenolic antibacterial triclosan. Int. J. Cosmetic Sci. 26, 111–116 (2004).

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Acknowledgements

The authors thank IOTA NanoSolutions Limited for an Industrial Senior Research Fellowship (S.R.), the Royal Society for a University Research Fellowship (A.C.) and an Industry Fellowship (S.R.) and Research Councils UK for an Academic Fellowship (H.Z.). We also acknowledge the Centre for Materials Discovery (University of Liverpool) for access to analytical equipment and specifically J. Weaver for help conducting surface tension measurements. The EPSRC (grant GR/N39999/01 and Portfolio Partnership in Complex Materials Discovery EP/C511794/1), IOTA NanoSolutions Limited and Unilever are thanked for financial support.

Author information

All authors contributed to the experimental programme, either through design of the experiment or practice. D.T. led the microbiological testing. H.Z., A.C. and S.R. co-wrote the manuscript.

Correspondence to Andrew I. Cooper or Steven P. Rannard.

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