Microencapsulation of antigens using biodegradable polyesters: facts and phantasies.

Abstract

New vaccination approaches and new delivery systems have been subject of intensive research activities recently. Controlled release vaccine delivery systems depend on the microencapsulation of antigens into biodegradable polymers, yielding small spherical polymeric particles, in the size range of 1-100 microns. By manipulating the micromorphology of the microparticles and degradation properties of the polymer either continuous or pulsatile release patterns can be adjusted. As biodegradable polymers mainly copolymers of lactic- and glycolic acid have been utilized, since these materials are known to be biocompatible and non-toxic. Apart from modulation of antigen release, an improvement of the adjuvant effect and an increase of in vitro (shelf-life) and in vivo stability of the antigen are issues of general interest with respect to parenteral vaccine delivery systems. Using different microparticles that release antigens in a pulsatile pattern at predetermined timepoints one hopes to induce protective immunity by a single administration of the vaccine delivery system. Using tetanus toxoid (TT) as a model antigen we have examined the stability during preparation, in vitro release and storage of TT microparticles. TT is a complex protein mixture sensitive to changes in pH conditions (pH < 5) and to thermal stress. TT microparticles can be prepared by a W/O/W double emulsion technique with satisfactory encapsulation efficiencies in good yields. In accordance with other investigators we observe an adjuvant effect of TT microspheres in mice upon sc administration leading to a long-lasting antibody response. In challenge experiments we could demonstrate a protective effect. The issue of an ideal release pattern remains open, since a boosting of the antibody titers during the bioerosion of the TT microspheres was not observed, possibly due to desactivation of TT in the degrading microspheres.