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Controlled release of NFκB decoy oligonucleotides from biodegradable polymer microparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
13742 897 2002 10 PDF Available
Title
Controlled release of NFκB decoy oligonucleotides from biodegradable polymer microparticles
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 10 wt%), ODN loading densities (0.4, 4, and 40 μg/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.

Keywords
Phosphorothioated decoy oligonucleotides (ODNs); Poly(dl-lactic-co-glycolic acid) (PLGA); Poly(ethylene glycol) (PEG); Controlled release; Biodegradable microparticles; Nuclear factor-kappa B (NFκB)
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Controlled release of NFκB decoy oligonucleotides from biodegradable polymer microparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 23, Issue 13, July 2002, Pages 2683–2692
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us