Poly-DL-lactide-poly (ethylene glycol) microspheres as oral and parenteraldelivery systems for hepatitis B surface antigen

This project was aimed at illustrating the potential Use of poly-DL-lactide -poly(ethylene glycol) (PELA) microspheres as a hepatitis B surface antigen (HBsAg) delivery system following subcutaneous (s.c.) or oral immunization over the current injection of an alum-absorbed antigen. The antigen-loadin g microspheres were elaborated by the solvent-extraction method based on th e formation of modified multiple w/o/w, emulsion. The microspheres were cha racterized by their particle size, HBsAg entrapment, and in vitro HBsAg rel ease behavior. Balb/c mice were immunized with an s.c. injection and oral a dministration of a single dose and two doses of a microsphere formulation. For comparison, the alum-absorbed HBsAg-immunized mice had a following intr amuscular (i.m.) injection at weeks 0 and 4. At weeks 8, 10, 14, and 24 pos tadministration, the blood and saliva samples were collected and detected b y the enzyme-linked immunosorbed assay (ELISA) method. A single injection o f HBsAg/PELA microspheres could induce a serum IgG antibody level comparabl e to the two-injection alum-absorbed HBsAg at the 14th week and higher than that at the 24th week. The saliva IgA of peroral groups was significantly higher than that of the s.c. injection of a microsphere formulation and i.m . injection of soluble antigen. These preliminary results demonstrated the potential of oral administration of antigen-loading microspheres in the ind uction of a secretary immune response, and it is suggested that a single-do se s.c. injection of antigen-loading microspheres would be an efficient imm unization schedule to elicit a protective response. (C) 2002 John Wiley & S ons, Inc. J Appl Polym Sci 83: 850-856, 2002.