Oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin as vaccine formulation: particle size...

The objective of the present study was to produce ovalbumin (OVA) loaded poly(lactide-co-glycolide) (PLGA) microspheres with different diameters and to evaluate their possibilities as vaccine formulation in mice following oral inoculation. Four kinds of OVA loaded PLGA microspheres with different mean average volume diameters (1.3, 4.0, 7.5, and 14.0 microns) were manufactured using a w/o/w emulsion/solvent evaporation method. Low loading efficiencies (8-20% w/w) were observed in all batches although smooth spherical particles were obtained. Single oral administrations of OVA loaded PLGA microspheres with different diameters to mice produced immune responses (serum IgG levels by ELISA) which were statistically higher than OVA solution as negative control (Fisher's paired t-test). A dose-response was observed, and single and double inoculation orally produced similar serum antibody levels. The rank of immune response was as follows: 4.0 microns- > 1.3 microns- = 7.5 microns- > 14.0 microns-microspheres. The oral inoculation with 0.13% OVA loaded PLGA microspheres having a mean volume diameter of 4.0 microns exhibited the best immune responses with values greater than those obtained after subcutaneous inoculation with complete Freund's adjuvant (CFA) as positive control, and not significantly different from those obtained after subcutaneous inoculation with the same microspheres.