Formulation and Characterization of Antigen-loaded PLGA Nanoparticles for Efficient Cross-priming of the Antigen
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Background: Nanoparticles (NPs) prepared from biodegradable polymers, such as poly (D,L-lactic acid-co-glycolic acid)(PLGA), have been studied as vehicles for the delivery of antigens to phagocytes. This paper describes the preparation of antigen-loaded PLGA-NPs for efficient cross-priming. Methods: NPs containing a similar amount of ovalbumin (OVA) but different sizes were produced using a micromixer-based W/O/W solvent evaporation procedure, and the efficiency of the NPs to induce the cross-presentation of OVA peptides were examined in dendritic cells (DCs). Cellular uptake and biodistribution studies were performed using fluorescein isothiocyanate (FITC)-loaded NPs in mice. Results: The NPs in the range of 1.1∼1.4μm in size were the most and almost equally efficient in inducing the crosspresentation of OVA peptides via H-2Kb molecules. Cellular uptake and biodistribution studies showed that opsonization of the NPs with mouse IgG greatly increased the percentage of FITC-positive cells in the spleen and lymph nodes. The major cell type of FITC-positive cells in the spleen was macrophages,whereas that of lymph nodes was DCs. Conclusion:These results show that IgG-opsonized PLGA-NPs with a mean size of 1.1μm would be the choice of biodegradable carriers for the targeted-delivery of protein antigens for cross-priming in vivo.
Abstract
Background: Nanoparticles (NPs) prepared from biodegradable polymers, such as poly (D,L-lactic acid-co-glycolic acid)(PLGA), have been studied as vehicles for the delivery of antigens to phagocytes. This paper describes the preparation of antigen-loaded PLGA-NPs for efficient cross-priming. Methods: NPs containing a similar amount of ovalbumin (OVA) but different sizes were produced using a micromixer-based W/O/W solvent evaporation procedure, and the efficiency of the NPs to induce the cross-presentation of OVA peptides were examined in dendritic cells (DCs). Cellular uptake and biodistribution studies were performed using fluorescein isothiocyanate (FITC)-loaded NPs in mice. Results: The NPs in the range of 1.1∼1.4μm in size were the most and almost equally efficient in inducing the crosspresentation of OVA peptides via H-2Kb molecules. Cellular uptake and biodistribution studies showed that opsonization of the NPs with mouse IgG greatly increased the percentage of FITC-positive cells in the spleen and lymph nodes. The major cell type of FITC-positive cells in the spleen was macrophages,whereas that of lymph nodes was DCs. Conclusion:These results show that IgG-opsonized PLGA-NPs with a mean size of 1.1μm would be the choice of biodegradable carriers for the targeted-delivery of protein antigens for cross-priming in vivo.
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