Novel method for concentrating and drying polymeric nanoparticles: Hydrogen bonding coacervate precipitation

Suzanne M. D'Addio, Concepcion Kafka, Mustafa Akbulut, Patrick Beattie, Walid Saad, Margarita Herrera, Michael T. Kennedy, Robert K. Prud'Homme

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Nanoparticles have significant potential in therapeutic applications to improve the bioavailability and efficacy of active drug compounds. However, the retention of nanometer sizes during concentrating or drying steps presents a significant problem. We report on a new concentrating and drying process for poly(ethylene glycol) (PEG) stabilized nanoparticles, which relies upon the unique pH sensitive hydrogen bonding interaction between PEG and polyacid species. In the hydrogen bonding coacervate precipitation (HBCP) process, PEG protected nanoparticles rapidly aggregate into an easily filterable precipitate upon the addition various polyacids. When the resulting solid is neutralized, the ionization of the acid groups eliminates the hydrogen bonded structure and the ∼100 nm particles redisperse back to within 10% of their original size when poly(acrylic acid) and citric acid are used and 45% when poly(aspartic acid) is used. While polyacid concentrations of 1-5 wt % were used to form the precipitates, the incorporation of the acid into the PEG layer is approximately 1:1 (acid residue):(ethylene oxide unit) in the final dried precipitate. The redispersion of dried β-carotene nanoparticles protected with PEG-b-poly(lactide-co-glycolide) polymers dried by HBCP was compared with the redispersion of particles dried by freeze-drying with sucrose as a cryprotectant, spray freeze-drying, and normal drying. Freeze-drying with 0, 2, and 12 wt % sucrose solutions resulted in size increases of 350%, 50%, and 6%, respectively. Spray freeze-drying resulted in particles with increased sizes of 50%, but no cryoprotectant and only moderate redispersion energy was required. Conventional drying resulted in solids that could not be redispersed back to nanometer size. The new HBCP process offers a promising and efficient way to concentrate or convert nanoparticle dispersions into a stable dry powder form.

Original languageEnglish (US)
Pages (from-to)557-564
Number of pages8
JournalMolecular Pharmaceutics
Issue number2
StatePublished - Apr 5 2010

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Medicine
  • Pharmaceutical Science


  • Aggregation
  • Citric acid
  • Coacervate
  • Drying
  • Hydrogen bonding
  • Lyophilization
  • Nanoparticle
  • Poly(acrylic acid)
  • Poly(aspartic acid)
  • Polymeric nanoparticles
  • Redispersion


Dive into the research topics of 'Novel method for concentrating and drying polymeric nanoparticles: Hydrogen bonding coacervate precipitation'. Together they form a unique fingerprint.

Cite this