Development of polymeric nanoparticles showing tuneable pH-responsive precipitation

Research Paper


A reverse micellar system comprising dioctyl-sulfosuccinate (AOT)/toluene was used as a template for polymerization of acrylamide/bisacrylamide-based functionalized polymeric nanoparticles. Such nanoparticles were typically sized between 20 and 90 nm and could be synthesized with a wide range of functional groups according to the monomers added to the polymerization mixture. Carboxy nanoparticles with acrylic acid as the functional monomer were synthesized in the reported work. The carboxy nanoparticles were pH sensitive and precipitated at pHs below 4. Modification of carboxy-functionalized polymeric nanoparticles with polyetheleneimine (PEI) resulted in the fabrication of a series of pH-responsive nanoparticles which could precipitate at different pHs and ionic strengths according to the PEI/carboxy ratio in the system. Both non-covalent PEI-nanoparticles conjugates and nanoparticles with covalently linked PEI behaved in this way.


Nanoparticles Polymeric Reverse micelles Stimuli-responsive pH-responsive 



The work reported has been carried out with financial assistance from the EC, project COMBIO (contract COOP-CT-2006-032628). We thank the Electron Microscopy Unit at Michael Smith Building of Manchester University, and Roger Meadows for performing the freeze-fracture of nanoparticles samples.


  1. Arizaga A, Ibarz G, Piñol R (2010) Stimuli-responsive poly(4-vinyl pyridine) hydrogel nanoparticles: synthesis by nanoprecipitation and swelling behavior. J Colloid Interface Sci 348:668–672. doi: 10.1016/j.jcis.2010.05.051 CrossRefGoogle Scholar
  2. Bae YH (1997) In: Park K (ed) Controlled drug delivery challenges and strategies. ACS, Washington, DCGoogle Scholar
  3. Benoit JP, Couvreur P, Devissaguet JP, Fessi H, Puisieux F, Roblot-Treupel L (1986) Les formes vectorisées ou distribution modulée, nouveuax sistèmes d’administration medicaments. J Pharm Belg 41:319–329Google Scholar
  4. Filippov S, Hruby M, Konak C, Mackova H, Spirkova M, Stepanek P (2008) Novel pH-responsive nanoparticles. Langmuir 24:9295–9301. doi: 10.1021/la801472x CrossRefGoogle Scholar
  5. Fujii M, Taniguchi M (1991) Application of reversibly soluble polymers in bioprocessing. Trends Biotechnol 9:191–196. doi: 10.1016/0167-7799(91)90062-M CrossRefGoogle Scholar
  6. Galaev IY, Mattiasson B (1999) ‘Smart’ polymers and what they could do in biotechnology and medicine. Trends Biotechnol 17:335–340. doi: 10.1016/S0167-7799(99)01345-1 CrossRefGoogle Scholar
  7. Galaev IY, Gupta MN, Mattiasson B (1996) Use smart polymers for bioseparations. ChemTech 12:19–25Google Scholar
  8. Guoquiang D, Batra R, Kaul R, Gupta MN, Mattiassion B (1995) Alternative modes of precipitation of Eudragit S 100: a potential ligand carrier for affinity precipitation of protein. Bioseparation 5:339–350Google Scholar
  9. Gurny R, Junginger HE, Pulsatile PN (1993) Drug delivery: current applications and future trends. Wissenschaftliche Verlagsgesellschaft, StuttgartGoogle Scholar
  10. Hui CL, Li XG, Hsing IM (2005) Well-dispersed surfactant-stabilized Pt/C nanocatalysts for fuel cell application: dispersion control and surfactant removal. Electrochim Acta 51:711–719. doi: 10.1016/j.electacta.2005.05.024 CrossRefGoogle Scholar
  11. Kumar A, Srivastava A, Galaev IY, Mattiasson B (2007) Smart polymers: physical forms and bioengineering applications. Prog Polym Sci 32:1205–1237. doi: 10.1016/j.progpolymsci.2007.05.003 CrossRefGoogle Scholar
  12. Langer R (1998) Drug delivery and targeting. Nature 392(Suppl.):5–10Google Scholar
  13. Martin GR, Jain RK (1994) Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy. Cancer Res 54:5670–5674Google Scholar
  14. McClean S, Prosser E, Meehan E, O’Malley D, Clarke N, Ramtoola Z (1998) Binding and uptake of biodegradable poly-dl-lactide micro- and nanoparticles in intestinal epithelia. Eur J Pharm Sci 6:153–163. doi: 10.1016/S0928-0987(97)10007-0 CrossRefGoogle Scholar
  15. Medeiros SF, Santos AM, Fessi H, Elaissari A (2011) Stimuli-responsive magnetic particles for biomedical applications. Int J Pharm 403:139–161. doi: 10.1016/j.ijpharm.2010.10.011 CrossRefGoogle Scholar
  16. Morrison RT, Boyd RN (1992) Organic Chemistry, 6th edn. Prentice-Hall Inc, New JerseyGoogle Scholar
  17. Motornov M, Roiter Y, Tokarev I, Minko S (2010) Stimuli-responsive nanoparticles, nanogels and capsules for integrated multifunctional intelligent systems. Prog Polym Sci 35:174–211. doi: 10.1016/j.progpolymsci.2009.10.004 CrossRefGoogle Scholar
  18. Qiu Y, Park K (2001) Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev 53:321–339. doi: 10.1016/S0169-409X(01)00203-4 CrossRefGoogle Scholar
  19. Sahoo SK, De TK, Ghosh PK, Maitra A (1998) pH- and Thermo-sensitive Hydrogel Nanoparticles. J Colloid Interface Sci 206:361–368CrossRefGoogle Scholar
  20. Sherwood L (1997) Human physiology from cells to systems, 3rd edn. Wadsworth Publishing Company, Belmont, pp 121–165Google Scholar
  21. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20. doi: 10.1016/S0168-3659(00)00339-4 CrossRefGoogle Scholar
  22. Vakurov A, Pchelintsev N, Forde J, O’Fagain C, Gibson T, Millner PA (2009) The preparation of size-controlled functionalized polymeric nanoparticles in micelles. Nanotechnology 20:295605. doi: 10.1088/0957-4484/20/29/295605 CrossRefGoogle Scholar
  23. Valeur B, Keh E (1979) Determination of the hydrodynamic volume of inverted micelles containing water by the fluorescent polarization technique. J Phys Chem 83:3305–3307. doi: 10.1021/j100488a025 CrossRefGoogle Scholar
  24. Wu XY, Zhang Q, Arshady R (2003) Stimuli sensitive hydrogels. Polymer structure and phase transition. In: Arshady R (ed) Polymeric biomaterials. Citus Books, LondonGoogle Scholar
  25. Zhang K, Wu XY (2004) Temperature and pH-responsive polymeric composite membranes for controlled delivery of proteins and peptides. Biomaterials 25:5281–5291. doi: 10.1016/j.biomaterials.2003.12.032 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Research Institute of Membrane and Systems Biology, University of LeedsLeedsUK

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