title: Predicting protein instability in sustained protein delivery systems using spectral-phase interference.
abstract: Biodegradable and non-biodegradable polymers represent promising materials for sustained protein delivery systems. However, structural protein instabilities due to interactions with the polymer surface are often observed. Aim of the present study was to analyze and predict these instabilities by determination of adsorption pattern and extent via biomolecular interaction analysis. A new optical method based on spectral-phase interference successfully demonstrated its suitability for this new application scope. It was characterized in terms of sensitivity, reproducibility and dynamic range using bovine serum albumin (BSA) as model compound. For protein-polymer interaction studies, materials with different wettabilities and zeta potential were selected and successfully applied on the sensor chip: Glass, poly(styrene), poly(lactic acid), poly(lactic-co-glycolic acid), and poly(ethylene carbonate). Concentration dependent adsorption curves revealed two principal adsorption patterns based on the connection between BSA spreading and supply rate. This connection was stronger influenced by polymer hydrophobicity than surface charge. Association, dissociation and binding rate constants in the range from 0.15 to 34.19 × 10(-6) M were obtained. Atomic force microscopy images of the films before and after adsorption confirmed the previous elaborated model. Poly(ethylene carbonate) emerged as highly promising biomaterial for protein delivery due to its favorable adsorption behavior based on low polymer-protein interactions.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-University Marburg, Ketzerbach 63, D-35032 Marburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Seidel
authors.forename: Johannes
authors.initials: J
authors.lastname: Sitterberg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vornholt
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
authors.forename: Michael
authors.initials: M
authors.lastname: Keusgen
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002417:Cattle; D016503:Drug Delivery Systems; D004867:Equipment Design; D005898:Glass / Q000737:chemistry; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D018625:Microscopy, Atomic Force / Q000379:methods; D011091:Polyesters; D011095:Polyethylenes / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; D011095:Polyethylenes; D011108:Polymers; D011137:Polystyrenes; D011506:Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C039212:polyethylene carbonate; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; C033616:poly(lactide)