Drug-Induced Morphology Switch in Drug Delivery Systems Based on Poly(2-oxazoline)s

Content Provider	Semantic Scholar
Author	Schulz, Anita Jaksch, Sebastian Schubel, René Wegener, Erik Di, Zhenyu Han, Yingchao Meister, Annette Kressler, Jörg Kabanov, Alexander V. Luxenhofer, Robert Papadakis, Christine M. Jordan, Rainer
Copyright Year	2014
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.
Starting Page	2686
Ending Page	2696
Page Count	11
File Format	PDF HTM / HTML
DOI	10.1021/nn406388t
PubMed reference number	24548260
Journal	Medline
Volume Number	8
Alternate Webpage(s)	https://tu-dresden.de/mn/chemie/mc/mc1/ressourcen/dateien/publikationen/download/bis-2015/schulz14.pdf?lang=en
Alternate Webpage(s)	http://ftp.ncbi.nlm.nih.gov/pub/pmc/2e/20/nn406388t.PMC4004286.pdf
Alternate Webpage(s)	https://doi.org/10.1021/nn406388t
Journal	ACS nano
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article