Particle size studies for subcutaneous delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin as vaccine formulation.
The primary objectives of the present study were to produce poly(lactide-co-glycolide) (PLGA) microspheres with different diameters, to characterize these microspheres which were loaded with a model antigen, ovalbumin 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 microns 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 expected burst release with all batches and the extent of the burst release increased with decreasing diameters of spheres; PLGA microspheres with the smallest diameter (1.2 microns) showed an 80% burst release within one day. Approximately 10-60% of ovalbumin remained unreleased 30 days later. The single subcutaneous administrations of ovalbumin-loaded PLGA microspheres with different diameters to mice induced good antibody responses above ovalbumin saline negative controls at 3, 6, 9, and 12 weeks after inoculation. Especially, 0.16% ovalbumin-loaded PLGA microspheres having mean volume diameter of 3.5 microns exhibited the best immune responses with values greater than those 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.
Uchida
T
T
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Goto
S
S
Foster
T P
TP
D000534:Alum Compounds / Q000737:chemistry; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant / Q000737:chemistry; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D014614:Vaccines, Synthetic / Q000737:chemistry*
D000534:Alum Compounds; D011108:Polymers; D014614:Vaccines, Synthetic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C041524:aluminum sulfate; D010047:Ovalbumin; D005620:Freund's Adjuvant