title: 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.
authors.affiliation: Department of Chemistry and Applied BioSciences, Drug Formulation & Delivery Group, Swiss Federal Institute of Technology Zurich, ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Barnali
authors.initials: B
authors.lastname: Mandal
authors.forename: Martina
authors.initials: M
authors.lastname: Kempf
authors.forename: Hans P
authors.initials: HP
authors.lastname: Merkle
authors.forename: Elke
authors.initials: E
authors.lastname: Walter
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000737:chemistry; D000536:Aluminum Hydroxide / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D011094:Polyethyleneimine / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties; D014612:Vaccines / Q000737:chemistry*
chemical_list: D000277:Adjuvants, Pharmaceutic; D004337:Drug Carriers; D011108:Polymers; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000536:Aluminum Hydroxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011094:Polyethyleneimine