title: Novel polymeric micelles for drug delivery: Material characterization and formulation screening.
abstract: A rising number of new chemical entities that exhibit only poor aqueous solubility are identified in drug discovery processes. Polymeric micelles composed of block copolymers (BP) facilitate the delivery of such lipophilic molecules in drug therapy. Consequently, a rational screening and selection procedure for novel BP was established. Further, the interplay of polymer structure, micelle formation and drug binding was studied. Therefore seven polymers (BP001 to BP007) were synthesized from different monomer compositions resulting in nanocarriers varying in surface decoration and lipophilicity. These polymers were characterized by H(1)-NMR and SEC. The molecular weight was ranging between 13 and 37kDa. The critical micelle concentration and micellar integrity in presence of human plasma were determined. Micelles were loaded with dexamethasone and characterized with regards to their size, morphology and surface charge. Polymeric micelles with a size of 49.21-236.37nm were obtained. A half-life of 11h was determined for five of the copolymers in presence of human plasma. Two nanocarrier formulations (BP006 and BP007) were exhibiting optimal micellar integrity in vitro and a modified release profile under biorelevant conditions. Strongest drug-polymer interaction was observed for nanocarrier compositions providing benzyl and carboxylic groups and were composed of BP006 and BP007.
authors.affiliation: Goethe University, Institute of Pharmaceutical Technology, D-60438 Frankfurt, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Janas
authors.affiliation: Goethe University, Institute of Pharmaceutical Technology, D-60438 Frankfurt, Germany.
authors.forename: Zouhair
authors.initials: Z
authors.lastname: Mostaphaoui
authors.affiliation: Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Schmiederer
authors.affiliation: Merck KGaA, Frankfurter Straße 250, D-64293, Darmstadt, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Fraunhofer-Institute for Molecular Biology and Applied Ecology, Project Group for Translational Medicine & Pharmacology, D-60438 Frankfurt, Germany. Electronic address: matthias.wacker@ime.fraunhofer.de.
authors.forename: Matthias G
authors.initials: MG
authors.lastname: Wacker
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006207:Half-Life; D006801:Humans; D008823:Micelles; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers
keywords: ATRP; Block copolymer synthesis; Dexamethasone; Drug delivery; Polymeric micelles