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Chitosan-coated poly(lactide-co-glycolide) nanoparticles for DNA delivery

Posted on:2008-08-13Degree:Ph.DType:Dissertation
University:University of Illinois at Chicago, Health Sciences CenterCandidate:Guo, ChunqiangFull Text:PDF
GTID:1444390005958711Subject:Health Sciences
Abstract/Summary:
Chitosan-coated poly(lactide-co-glycolide) nanoparticles (chitosan- PLGA NPs), a cationic nanoparticulate system was evaluated for DNA delivery. Electrostatic interactions between chitosan and PLGA, cationic nanoparticles and DNA are the primary mechanistic basis for this delivery system. Chitosan-PLGA NPs were prepared in various concentrations of chitosan using single emulsion-solvent evaporation technique. The physical properties of chitosan-PLGA varied with concentrations of chitosan in terms of particle size, zeta potential and coated chitosan. The mechanism of chitosan adsorption on PLGA NPs was considered to be a multilayer behavior, as elucidated by various adsorption isotherms. In addition, the adsorption of chitosan can be affected by factors including pH and ionic strength.;The complexation of DNA with chitosan-PLGA NPs was influenced by stoichiometric ratio (N/P ratio), pH and ionic strength in combination with the properties (particle size, zeta potential and chitosan coating) of chitosan-PLGA NPs. Complexation of DNA with chitosan-PLGA NPs was further confirmed by agarose gel retardation and provided protective effect against DNase cleavage.;In vitro transfection efficiencies of chitosan-PLGA NPs were greatly affected by stoichiometric ratio, serum and pH, as well as the physical properties of chitosan-PLGA NPs. The transfection of GFP plasmid was enhanced in CHO cells compared to naked DNA and blank PLGA NPs. The transfection profiles were generally different from the complexation profiles of DNA and chitosan-PLGA NPs. However, the complexation data of DNA and chitosan-PLGA NPs provided useful information to interpret the transfection.;A comprehensive understanding of interaction between polyelectrolyte and polyesters materials will definitely be beneficial to the research employing particulate systems for gene therapy. To achieve high transfection efficiency, careful choice of various conditions is necessary to modulate the delivery system since intricate physical-chemical interactions play an important role.
Keywords/Search Tags:DNA, Chitosan, Delivery, PLGA nps, Nanoparticles, System
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