Controlled release of NFκB decoy oligonucleotides from biodegradable polymer microparticles

Xun Zhu, Lichun Lu, Bradford L. Currier, Anthony J. Windebank, Michael J. Yaszemski

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The objective of this study was to evaluate a poly(DL-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) delivery system for nuclear factor-kappa B (NFκB) decoy phosphorothioated oligonucleotides (ODNs). PLGA/PEG microparticles loaded with ODNs were fabricated with entrapment efficiencies up to 70%. The effects of PEG contents (0, 5, and 10wt%), ODN loading densities (0.4, 4, and 40μg/mg), and pH of the incubation medium (pH 5, 7.4, and 10) on ODN release kinetics from the PLGA/PEG microparticles were investigated in vitro for up to 28 days. The release profiles in pH 7.4 phosphate buffered saline (PBS) were characterized by an initial burst during the first 2 days, a linear release phase until day 18, and a final release phase for the rest of the period. Up to 85% of the ODNs were released after 28 days in pH 7.4 PBS regardless of the ODN loading density and PEG content. Higher ODN loading densities resulted in lower entrapment efficiencies and greater initial burst effects. The bulk degradation of PLGA was not significantly affected by the PEG content and ODN loading density, but significantly accelerated at acidic buffer pH. Under acidic and basic conditions, the aggregation of microparticles resulted in significantly lower cumulative mass of released ODNs than that released at neutral pH. The effects of pH were reduced by the incorporation of PEG into PLGA microparticles. Since the PLGA degradation products are acidic, PLGA/PEG microparticles might provide a better ODN delivery vehicle than PLGA microparticles. These results suggest that PLGA/PEG microparticles are useful as delivery vehicles for controlled release of ODNs and merit further investigation in cell culture and animal models of glioblastoma.

Original languageEnglish (US)
Pages (from-to)2683-2692
Number of pages10
JournalBiomaterials
Volume23
Issue number13
DOIs
StatePublished - May 14 2002

Keywords

  • Biodegradable microparticles
  • Controlled release
  • Nuclear factor-kappa B (NFκB)
  • Phosphorothioated decoy oligonucleotides (ODNs)
  • Poly(DL-lactic-co-glycolic acid) (PLGA)
  • Poly(ethylene glycol) (PEG)

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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