Potential of polymeric lamellar substrate particles (PLSP) as adjuvants for vaccines

In recent years microspheres or microparticles produced from biodegradable polymers such as poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) containing encapsulated vaccine antigens have been investigated for administration via parenteral, oral, and intranasal routes. These micropar ticles allow the controlled release of vaccines with an aim to reduce the n umber of doses for primary immunisation or to develop single dose vaccines. The polymer materials have been widely regarded as being of minimal toxici ty. Evaluation of candidate systems in animal studies have shown antibody l evels and cell responses similar to or greater than those observed with adj uvants such as alum. However, there are concerns regarding the integrity an d immunogenicity of the antigen during the encapsulation process when the a ntigen is exposed to organic solvents, high shear stresses and the exposure of antigen to low pH which is caused by polymer degradation. An alternativ e approach would be to adsorb antigens to the surface of biodegradable poly mer particles. Polymeric lamellar substrate particles (PLSP), produced by a simple precipitation of PLA, are suitable for this purpose. The adsorption of antigens onto these particles is a simple procedure. It avoids pH chang es due to bulk polymer degradation and the use of solvents and therefore wi ll be less damaging to the vaccine. Moreover, such systems will be much eas ier to scale up for a clinical study and eventual manufacture. The aim of t his article is to discuss the preparation and physical characteristics of P LSP, antigen adsorption, in vivo efficacy of PLSP antigen systems and to co nsider the potential of PLSP as controlled release adjuvants for protein, p eptide or viral vaccines. (C) 1999 Elsevier Science Ltd. All rights reserve d.