Polyelectrolyte stabilized drug nanoparticles via flash nanoprecipitation: A model study with β-carotene

Zhengxi Zhu, Katrin Margulis-Goshen, Shlomo Magdassi, Yeshayahu Talmon, Christopher W. Macosko

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95 Scopus citations


Polyelectrolyte protected β-carotene nanoparticles (nanosuspensions) with average diameter of <100 nm were achieved by turbulent mixing and flash nanoprecipitation (FNP). Three types of multi-amine functional polyelectrolytes, ε-polylysine (ε-PL), poly(ethylene imine) (PEI), and chitosan, were investigated to electrosterically protect the nanoparticles. Particle size and distribution were measured by dynamic light scattering (DLS); particles were imaged via scanning electron microscopy (SEM) and cryogenic transmission electron microscopy (cryo-TEM). Low pH and high polyelectrolyte molecular weight gave the smallest and most stable particles. High drug loading capacity, >80 wt%, was achieved by using either PEI or chitosan. X-ray diffraction (XRD) patterns showed that β-carotene nanoparticles were amorphous. These findings open the way for utilization of FNP for preparation of nanoparticles with enhanced bioavailability for highly water insoluble drugs.

Original languageAmerican English
Pages (from-to)4295-4306
Number of pages12
JournalJournal of Pharmaceutical Sciences
Issue number10
StatePublished - Oct 2010

Bibliographical note

Funding Information:
We thank Yutaka Miura at the University of Tokyo for characterizing ε-PL, Udaya Toti for HPLC measurement, Wei Fan for assisting in XRD measurement, Thomas Hoye and Jayanth Panyam for fruitful discussions, Michael Tsapatsis for the access of DLS apparatus, and Chisso Corporation for providing ε-PL. This work was supported by the National Science Foundation under the NIRT Program (Award Number CTS-0506966), IPRIME at the University of Minnesota, MRSEC at the University of Minnesota, and the Lady Davis Fellowship Foundation at the Technion. Parts of this work were carried out in the University of Minnesota, Institute of Technology Characterization Facility, which receives partial support from NSF through the NNIN program.


  • Biodegradable polymers
  • Formulation
  • Light-scattering
  • Mixing
  • Nanoparticles
  • Nanosuspensions
  • Polyelectrolytes
  • Polymeric drug delivery systems
  • Stabilization
  • Supersaturation


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