Immobilisation of GM-CSF onto particulate vaccine carrier systems

Abstract

Physical connection of vaccine carriers with immunostimulating cytokines may provide an interesting possibility to enhance the immune response of protective or therapeutic vaccines. As a first evaluation, various aluminium hydroxide adjuvants and poly( d, l-lactide- co-glycolide) (PLGA) microparticulates with modified positively and negatively charged surfaces were prepared to adsorb granulocyte-macrophage colony-stimulating factor (GM-CSF) under different pH conditions. Negatively charged surfaces were chosen to resemble physiological binding of GM-CSF to extracellular glycosaminoglycans, while modified positively charged surfaces may enhance GM-CSF adsorption due to electrostatic interaction. Release of GM-CSF was checked in vitro in a simulated interstitial environment. Anionic and cationic surfaces efficiently attracted GM-CSF to the carrier surface independently of the pH, while the composition of the carrier largely influenced the release of GM-CSF over time. Thus, the adsorption of GM-CSF to aluminium hydroxide adjuvants and PLGA microparticulates provides a simple and efficient possibility to physically connect the cytokine with these commonly used and potential vaccine carriers and may enable its localised delivery to the side of action.