Design and Characterisation of Poly(lactide-co-glycolide) Small Particulate Systems for the Delivery of Immunostimulant CpG Oligonucleotide
The aim of this study was to develop and characterize biodegradable small particles of poly(lactide-co-glycolide) (PLGA) as oral vehicle for immunostimulatory oligonucleotide (ODN-CpG). Three different polymers were used as surface stabilizing agents (SSA): polyvinyl alcohol (PVA), hydrophobically modified hydroxyethylcellulose (HMHEC), or polyethylenimine (PEI). Particle surface was characterized as well as ODN-CpG release kinetics. All particles were found to be around 1 μ. Particles of PLGA-PVA and PLGA-HMHEC were spherical in shape with a smooth surface whereas PLGA-PEI particles were porous. The presence of ODN-CpG within the particle matrix was confirmed in all particle type using scanning laser confocal microscopy. Particle surface assayed by XPS, zeta potential analysis, and evaluation of particle surface hydrophobicity suggested that a significant amount of SSA remains associated onto particle surface. Release profiles evidenced that ODN-CpG release was strongly dependent on particle surface properties. 100% of encapsulated ODN-CpG was released from PLGA-PVA and PLGA-HMHEC particles 37 days after incubation in a buffer solution, whereas only 25% were released from PLGA-PEI particles. ODN-CpG can therefore be nicely entrapped in several types of small particles displaying a prolonged and controlled release upon time. In addition, particle surface is not modified by the presence of ODN-CpG.
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Document Type: Research Article
Publication date: September 1, 2006
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