Comparison of poly(acryl starch) and poly(lactide-co-glycolide) microspheres as drug delivery system for a rotavirus vaccine.
Drug delivery systems allowing controlled release of antigen are of particular interest in the development of vaccines. We have compared poly(acrylic starch) microspheres (PAS) and poly(lactide-co-glycolide) microspheres (PLG) as drug delivery systems for a rotavirus vaccine. The polymers are both biodegradable but have different degradation mechanisms and antigen release profiles. PAS are enzymatically degraded and have a continuous fast antigen release rate compared to the hydrolytically degraded PLG which release the incorporated antigen in a pulsatile manner. In this study mice were immunised intramuscularly and orally on three occasions with formalin-inactivated rotavirus (FRRV) incorporated in PAS and PLG and with FFRV alone. Serum and faeces samples were collected and analysed by ELISA for rotavirus specific IgG and IgA antibodies. A neutralising assay was also conducted on both serum and faeces antibodies. The two different polymer drug delivery systems induced different immune responses depending on administration route. PAS elicited significant antibody levels and neutralising effect after oral administration while PLG showed high antibody levels after intramuscular administration. The immune response appears to be dependent on the differences in antigen release and degradation mechanism for the two polymer systems.
Sturesson
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Department of Pharmacy, Uppsala University, Box 580, SE-751 23, Uppsala, Sweden.
Degling Wikingsson
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D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D019344:Lactic Acid / Q000737:chemistry*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012401:Rotavirus / Q000276:immunology*; D013213:Starch / Q000031:analogs & derivatives* / Q000737:chemistry; D013462:Sulfur Radioisotopes; D015164:Vaccines, Inactivated / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000914:Antibodies, Viral; D004337:Drug Carriers; D007070:Immunoglobulin A; D011108:Polymers; D013462:Sulfur Radioisotopes; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013213:Starch; C043831:starch polyacrylate