The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups

D. Neradovic, O. Soga, C.F. Van Nostrum, W.E. Hennink

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Block copolymers of poly(ethylene glycol) (PEG) as a hydrophilic block and N-isopropylacrylamide (PNIPAAm) or poly (NIPAAm-co-N-(2-hydroxypropyl) methacrylamide-dilactate) (poly(NIPAAm-co-HPMAm-dilactate)) as a thermosensitive block, are able to self-assemble in water into nanoparticles above the cloud point (CP) of the thermosensitive block. The influence of processing and the formulation parameters on the size of the nanoparticles was studied using dynamic light scattering. PNIPAAm-b-PEG 2000 polymers were not suitable for the formation of small and stable particles. Block copolymers with PEG 5000 and 10000 formed relatively small and stable particles in aqueous solutions at temperatures above the CP of the thermosensitive block. Their size decreased with increasing molecular weight of the thermosensitive block, decreasing polymer concentration and using water instead of phosphate buffered saline as solvent. Extrusion and ultrasonication were inefficient methods to size down the polymeric nanoparticles. The heating rate of the polymer solutions was a dominant factor for the size of the nanoparticles. When an aqueous polymer solution was slowly heated through the CP, rather large particles (≥200nm) were formed. Regardless the polymer composition, small nanoparticles (50-70nm) with a narrow size distribution were formed, when a small volume of an aqueous polymer solution below the CP was added to a large volume of heated water. In this way the thermosensitive block copolymers rapidly pass their CP ('heat shock' procedure), resulting in small and stable nanoparticles. © 2003 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)2409-2418
Number of pages10
JournalBiomaterials
Volume25
Issue number12
DOIs
Publication statusPublished - 1 May 2004

Keywords

  • Heating rate
  • Nanoparticles
  • Poly(ethylene glycol)
  • Poly(N-isopropylacrylamide)
  • Size control
  • acrylic acid copolymer
  • macrogol
  • macrogol 10000
  • macrogol 5000
  • nanoparticle
  • phosphate
  • poly(n isopropylacrylamide)
  • sodium chloride
  • solvent
  • unclassified drug
  • water
  • aqueous solution
  • article
  • concentration (parameters)
  • drug formulation
  • hydrolysis
  • light scattering
  • molecular weight
  • priority journal
  • temperature

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