title: Surface modification of PLGA particles: the interplay between stabilizer, ligand size, and hydrophobic interactions.
abstract: Therapeutic and diagnostic carriers can be functionalized with active targeters to induce tissue-specific delivery. However, the possible impact of adsorbed steric stabilizer such as the frequently used poloxamers (Pluronics) on surface modification of poly(D,L-lactide-co-glycolide) (PLGA) particles has not been examined so far. Therefore, three model ligands of different molecular weights (653; 36,000; 155,000 g/mol) covering the size range of important targeters were conjugated to the surface of PLGA microparticles in the presence of different concentrations of Pluronic F68 (0.01-5%, w/v). Flow cytometry and fluorimetric quantification revealed for all tested ligands that high Pluronic concentrations decreased the coupling efficiency to a half or even one-third of that achieved in the absence of stabilizer. Moreover, the reduction strongly depends on the ligand size and its propensity for hydrophobic interactions. Apart from that, a high degree of particle aggregation was observed with Pluronic concentrations below 0.1% (w/v). Thus, a compromise has to be found, which combines sufficient stability with the best possible ligand coupling efficiency. For the studied system, 0.1% (w/v) turned out to be the optimum concentration of Pluronic F68.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Ratzinger
authors.forename: Ursula
authors.initials: U
authors.lastname: Länger
authors.forename: Lukas
authors.initials: L
authors.lastname: Neutsch
authors.forename: Fritz
authors.initials: F
authors.lastname: Pittner
authors.forename: Michael
authors.initials: M
authors.lastname: Wirth
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
mesh_terms: D000818:Animals; D002103:Cadaverine / Q000737:chemistry; D005434:Flow Cytometry; D019793:Fluorescein / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D055767:Immobilized Proteins / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D008024:Ligands; D020442:Poloxamer / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D005456:Fluorescent Dyes; D055767:Immobilized Proteins; D007074:Immunoglobulin G; D008024:Ligands; D020442:Poloxamer; D011098:Polyglactin 910; D002103:Cadaverine; D019793:Fluorescein