title: Charged nanoparticles as protein delivery systems: a feasibility study using lysozyme as model protein.
abstract: The aim of this study was to investigate the feasibility of negatively charged nano-carriers (nanoparticles), consisting of polymer blends of poly(lactide-co-glycolide) (PLGA) and poly(styrene-co-4-styrene-sulfonate) (PSS), to improve the loading capacity and release properties of a positively charged model protein, lysozyme, through an adsorption process. Nanoparticles were prepared by a solvent displacement method and characterized in terms of size, zeta-potential, morphology, as well as loading capacity of model protein lysozyme. Morphology of these particles was investigated using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The loading capacity of lysozyme was evaluated as a function of polymer blend ratio, protein concentration, pH, and ionic strength; in vitro release profiles were also studied. The results show that negatively charged nanoparticles were obtained using polymer blends of PLGA and PSS, characterized by increased net negative surface charge with increasing ratios of PSS. Moreover, protein loading capacity increased as function of PSS/PLGA ratio. Increased pH facilitated the adsorption process and improved the loading capacity. Maximum loading efficiency was achieved at salt concentrations of 50mM. In vitro release of lysozyme from the polymer blend nanoparticles was dependent on drug loading and full bioactivity of lysozyme was preserved throughout the process. These findings suggest that this is a feasible method to prepare nanoparticles with high surface charge density to efficiently adsorb oppositely charged protein through electrostatic interactions.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps Universität of Marburg, Marburg, Germany.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
authors.forename: Erik
authors.initials: E
authors.lastname: Rytting
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Schaper
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009113:Muramidase / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D011506:Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C421864:hen egg lysozyme; D009113:Muramidase