An investigation of the factors controlling the adsorption of protein antigens to anionic PLG microparticles.
This work examines physico-chemical properties influencing protein adsorption to anionic PLG microparticles and demonstrates the ability to bind and release vaccine antigens over a range of loads, pH values, and ionic strengths. Poly(lactide-co-glycolide) microparticles were synthesized by a w/o/w emulsification method in the presence of the anionic surfactant DSS (dioctyl sodium sulfosuccinate). Ovalbumin (OVA), carbonic anhydrase (CAN), lysozyme (LYZ), lactic acid dehydrogenase, bovine serum albumin (BSA), an HIV envelope glyocoprotein, and a Neisseria meningitidis B protein were adsorbed to the PLG microparticles, with binding efficiency, initial release and zeta potentials measured. Protein (antigen) binding to PLG microparticles was influenced by both electrostatic interaction and other mechanisms such as van der Waals forces. The protein binding capacity was directly proportional to the available surface area and may have a practical upper limit imposed by the formation of a complete protein monolayer as suggested by AFM images. The protein affinity for the PLG surface depended strongly on the isoelectric point (pI) and electrostatic forces, but also showed contributions from nonCoulombic interactions. Protein antigens were adsorbed on anionic PLG microparticles with varying degrees of efficiency under different conditions such as pH and ionic strength. Observable changes in zeta potentials and morphology suggest the formation of a surface monolayer. Antigen binding and release occur through a combination of electrostatic and van der Waals interactions occurring at the polymer-solution interface.
Chesko
James
J
Vaccine Delivery Group, Chiron Corporation, 4560 Horton St., Emeryville, California 94608, USA. james_chesko@chiron.com
Kazzaz
Jina
J
Ugozzoli
Mildred
M
O'hagan
Derek T
DT
Singh
Manmohan
M
D000327:Adsorption; D000941:Antigens / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry; D016503:Drug Delivery Systems; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008863:Microspheres; D009113:Muramidase; D009994:Osmolar Concentration; D010047:Ovalbumin / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D013499:Surface Properties; D014612:Vaccines
D000941:Antigens; D015699:HIV Envelope Protein gp120; D011108:Polymers; D011506:Proteins; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin; D009113:Muramidase; D002256:Carbonic Anhydrases