Enhanced core hydrophobicity, functionalization and cell penetration of polybasic nanomatrices

Omar Z. Fisher, Timothy Kim, Stephen R. Dietz, Nicholas A. Peppas

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Purpose. In this work a novel pH-responsive nanoscale polymer network was investigated for potential applications in nanomedicine. These consisted of a polybasic core surface stabilized with poly(ethylene glycol) grafts. The ability to control swelling properties via changes in core hydrophobicity and crosslinking feed density was assessed. The nanomatrices were also evaluated in vitro as nanocarriers for targeted intracellular delivery of macromolecules. Materials and Methods. Photo-emulsion polymerization was used to synthesize poly[2-(diethylamino)ethyl methacrylate-co-t-butyl methacrylate-g-poly(ethylene glycol)] (PDBP) nanomatrices. These were characterized using NMR, dynamic and electrophoretic light scattering, electron microscopy. The cytocompatibility and cellular uptake of nanomatrices was measured using the NIH/3T3 and A549 cell lines. Results. PDBP nanomatrices had a dry diameter of 40-60 nm and a hydrodynamic diameter of 70-90 nm in the collapsed state. Maximum volume swelling ratios from 6-22 were obtained depending on crosslinking feed density. Controlling the hydrophobicity of the networks allowed for control over the critical swelling pH without a significant loss in maximal volume swelling. The effect of PDBP nanomatrices on cell viability and cell membrane integrity depended on crosslinking feed density. Cell uptake and cytosolic delivery of FITC-albumin was enhanced from clathrin-targeting nanocarriers. The uptake resulted in nuclear localization of the dye in a cell type dependent fashion. Conclusions. The results of this work indicate that PDBP nanomatrices have tunable swelling properties. The networks were cytocompatible and proved to be suitable agents for intracellular delivery.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalPharmaceutical Research
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Keywords

  • Cell uptake
  • Endosomolytic agent
  • Nanogel
  • Photopolymerization
  • pH-responsive

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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