Poly-DL-lactide-poly(ethylene glycol) microspheres as oral and parenteral delivery 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‐loading microspheres were elaborated by the solvent‐extraction method based on the formation of modified multiple w/o/w emulsion. The microspheres were characterized by their particle size, HBsAg entrapment, and in vitro HBsAg release behavior. Balb/c mice were immunized with an s.c. injection and oral administration of a single dose and two doses of a microsphere formulation. For comparison, the alum‐absorbed HBsAg‐immunized mice had a following intramuscular (i.m.) injection at weeks 0 and 4. At weeks 8, 10, 14, and 24 postadministration, the blood and saliva samples were collected and detected by the enzyme‐linked immunosorbed assay (ELISA) method. A single injection of HBsAg/PELA microspheres could induce a serum lgG antibody level comparable to the two‐injection alum‐absorbed HBsAg at the 14th week and higher than that at the 24th week. The saliva lgA 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 induction of a secretory immune response, and it is suggested that a single‐dose s.c. injection of antigen‐loading microspheres would be an efficient immunization schedule to elicit a protective response. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 850–856, 2002