title: Drug-induced morphology switch in drug delivery systems based on poly(2-oxazoline)s.
abstract: Defined aggregates of polymers such as polymeric micelles are of great importance in the development of pharmaceutical formulations. The amount of drug that can be formulated by a drug delivery system is an important issue, and most drug delivery systems suffer from their relatively low drug-loading capacity. However, as the loading capacities increase, i.e., promoted by good drug-polymer interactions, the drug may affect the morphology and stability of the micellar system. We investigated this effect in a prominent system with very high capacity for hydrophobic drugs and found extraordinary stability as well as a profound morphology change upon incorporation of paclitaxel into micelles of amphiphilic ABA poly(2-oxazoline) triblock copolymers. The hydrophilic blocks A comprised poly(2-methyl-2-oxazoline), while the middle blocks B were either just barely hydrophobic poly(2-n-butyl-2-oxazoline) or highly hydrophobic poly(2-n-nonyl-2-oxazoline). The aggregation behavior of both polymers and their formulations with varying paclitaxel contents were investigated by means of dynamic light scattering, atomic force microscopy, (cryogenic) transmission electron microscopy, and small-angle neutron scattering. While without drug, wormlike micelles were present, after incorporation of small amounts of drugs only spherical morphologies remained. Furthermore, the much more hydrophobic poly(2-n-nonyl-2-oxazoline)-containing triblock copolymer exhibited only half the capacity for paclitaxel than the poly(2-n-butyl-2-oxazoline)-containing copolymer along with a lower stability. In the latter, contents of paclitaxel of 8 wt % or higher resulted in a raspberry-like micellar core.
authors.affiliation: Professur für Makromolekulare Chemie, Department Chemie, Technische Universität Dresden , Mommsenstraße 4, 01069 Dresden, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Schulz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jaksch
authors.forename: Rene
authors.initials: R
authors.lastname: Schubel
authors.forename: Erik
authors.initials: E
authors.lastname: Wegener
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Di
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Han
authors.forename: Annette
authors.initials: A
authors.lastname: Meister
authors.forename: Jörg
authors.initials: J
authors.lastname: Kressler
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Robert
authors.initials: R
authors.lastname: Luxenhofer
authors.forename: Christine M
authors.initials: CM
authors.lastname: Papadakis
authors.forename: Rainer
authors.initials: R
authors.lastname: Jordan
mesh_terms: D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008958:Models, Molecular; D008968:Molecular Conformation; D010080:Oxazoles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry*; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008823:Micelles; D010080:Oxazoles; C577913:poly(2-oxazoline); D017239:Paclitaxel