T. Uchida et al., PARTICLE-SIZE STUDIES FOR SUBCUTANEOUS DELIVERY OF POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES CONTAINING OVALBUMIN AS VACCINE FORMULATION, Journal of Pharmacy and Pharmacology, 47(7), 1995, pp. 556-560
The primary objectives of the present study were to produce poly(lacti
de-co-glycolide) (PLGA) microspheres with different diameters, to char
acterize these microspheres which were loaded with a model antigen, ov
albumin and to evaluate the effect of microsphere particle size on the
serum antibody levels following administration to mice. Four kinds of
ovalbumin-loaded PLGA microspheres with different diameters (1.2, 3.5
, 7.0 and 14.3 mu m as mean volume diameter) were manufactured by a w/
o/w emulsion/solvent evaporation method. Low loading percent (0.08%-0.
25% w/w) and efficiencies (8-25% w/w) were observed. Examination using
scanning electron photomicrographs showed smooth spherical particles.
The in-vitro release of ovalbumin from microspheres showed an expecte
d burst release with all batches and the extent of the burst release i
ncreased with decreasing diameters of spheres; PLGA microspheres with
the smallest diameter (1.2 mu m) showed an 80% burst release within on
e day. Approximately 10-60% of ovalbumin remained unreleased 30 days l
ater. The single subcutaneous administrations of ovalbumin-loaded PLGA
microspheres with different diameters to mice induced good antibody r
esponses above ovalbumin saline negative controls at 3, 6, 9, and 12 w
eeks after inoculation. Especially, 0.16% ovalbumin-loaded PLGA micros
pheres having mean volume diameter of 3.5 mu m exhibited the best immu
ne responses with values greater than these obtained after inoculation
with adjuvants such as complete Freund's adjuvant or alum as positive
control. The strong adjuvant activity of PLGA microspheres as vaccine
formulation was suggested.