Composition and surface charge of DNA-loaded microparticles determine maturation and cytokine secretion in human dendritic cells.
OBJECTIVE
Biodegradable microparticles prepared from poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) have been shown to be promising carrier systems for vaccine delivery. Here, we have investigated the capacity of different PLA and PLGA microparticle formulations to induce stimulation of human blood monocyte-derived dendritic cells (DCs).


METHODS
Stimulation of human derived dendritic cells by plain microparticles were compared with microparticles loaded with plasmid DNA or double-stranded salmon DNA either by encapsulation or adsorption to the surface of cationic microparticles. Stimulation of DCs was monitored by the up-regulation of surface maturation markers CD83 and CD86 and the secretion of IL-12 and TNF-alpha.


RESULTS
Slowly degrading PLA microparticles did not induce any detectable stimulation or activation of DCs. In contrast, fast degrading PLGA microparticles were able to influence DC maturation and cytokine secretion dependent on their surface charge. Anionic PLGA microparticles induced an up-regulation of CD83 and high TNF-alpha secretion, which was further enhanced up to the level of the potent stimulator lipopolysaccharide (LPS) when plasmid DNA was encapsulated. Moreover, the secretion of significant amounts of IL-12 was observed. Cationic PLGA microparticles induced an up-regulation of CD86 and moderate TNF-alpha secretion, but no IL-12 secretion, with no additional effects in the presence of plasmid DNA.


CONCLUSIONS
The data suggest that the composition and charge of biodegradable DNA-loaded microparticles profoundly influences maturation and cytokine secretion in DCs. Thus, the individual formulation of microparticles used as a vaccine carrier system might considerably influence the profile of the immune response.
Jilek
Samantha
S
Department of Applied Biosciences, Swiss Federal Institute of Technology Zurich (ETH), Zurich, Switzerland.
Ulrich
Michael
M
Merkle
Hans P
HP
Walter
Elke
E
D001673:Biodegradation, Environmental; D002214:Capsules; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004337:Drug Carriers; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D010957:Plasmids; D011091:Polyesters / Q000737:chemistry* / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002214:Capsules; D016207:Cytokines; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D004247:DNA