PLG microparticles stabilised using enteric coating polymers as oral vaccine delivery systems

Novel poly(dl-lactide-co-glycolide) microparticles for oral vaccine deliver y were formulated using the enteric polymers Eudragit(R) L100-55 and carbox ymethylethylcellulose (CMEC) as stabilisers. To serve as a control, micropa rticles were also produced using the conventional PVA surfactant. In all th ree cases the antigen, ovalbumin (OVA)-loaded microparticles produced were less than 5 mu m in diameter and had a spherical, smooth rounded appearance . The presence of surfactants at the microparticle surface was demonstrated by the surface analysis techniques, XPS and SSIMS. Incubation of micropart icles with solutions of pepsin or trypsin led to the removal of a proportio n of the antigen associated with all three systems. However, in three CMEC- stabilised microparticle formulations and one of three Eudragit formulation s, a high percentage of the associated antigen was protected from removal b y a solution of pepsin at pH 1.2 compared with the PVA-stabilised micropart icles. In addition, with certain CMEC and Eudragit formulations a degree of protection was also afforded to the associated OVA against removal by tryp sin at pH 7.4. Following the incubation of microparticles in simulated gast ric fluid a higher percentage of intact antigenic OVA was detected in micro particles stabilised using CMEC than in the PVA- and Eudragit- stabilised f ormulations. Oral immunisation of mice with OVA-loaded microparticles stabi lised using either of the three surfactants led to the induction of specifi c serum IgG and salivary IgA antibodies. Significantly higher levels of spe cific salivary IgA antibody to OVA were measured in mice immunised with the CMEC-stabilised microparticles than with the other two formulations. This novel approach in PLG microparticle formulation may have potential in incre asing the efficacy of microparticulate systems for the oral administration of vaccines. (C) 1999 Published by Elsevier Science Ltd. All rights reserve d.