Star-Shaped Drug Carriers for Doxorubicin with POEGMA and POEtOxMA Brush-like Shells: A Structural, Physical, and Biological Comparison

• Published in: Biomacromolecules 2013-08, Vol.14 (8), p.2536-2548
• Main Authors: Knop, Katrin, Pretzel, David, Urbanek, Annett, Rudolph, Tobias, Scharf, Daniel H, Schallon, Anja, Wagner, Michael, Schubert, Stephanie, Kiehntopf, Michael, Brakhage, Axel A, Schacher, Felix H, Schubert, Ulrich S
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - metabolism; Antibiotics, Antineoplastic - pharmacology; Antineoplastic agents; Applied sciences; Biological and medical sciences; Chemotherapy; Doxorubicin - chemistry; Doxorubicin - metabolism; Doxorubicin - pharmacology; Drug Carriers; Drug Compounding; Erythrocytes - drug effects; Exact sciences and technology; Hemolysis; Humans; Hydrophobic and Hydrophilic Interactions; Kinetics; Materials Testing; MCF-7 Cells; Medical sciences; Molecular Conformation; Nanocapsules - chemistry; Organic polymers; Oxazoles - chemical synthesis; Particle Size; Pharmacology. Drug treatments; Physicochemistry of polymers; Platelet Activation - drug effects; Polyesters - chemistry; Polyethylene Glycols - chemical synthesis; Polymers with particular properties; Polymethacrylic Acids - chemical synthesis; Preparation, kinetics, thermodynamics, mechanism and catalysts; Solutions; Surface-Active Agents - chemistry
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm400091n

The synthesis of amphiphilic star-shaped poly(ε-caprolactone)-block-poly(oligo(ethylene glycol)methacrylate)s ([PCL18-b-POEGMA]4) and poly(ε-caprolactone)-block-poly(oligo(2-ethyl-2-oxazoline)methacrylate)s ([PCL18-b-POEtOxMA]4) is presented. Unimolecular behavior in aqueous systems is observed with the tendency to form loose aggregates for both hydrophilic shell types. The comparison of OEGMA and OEtOxMA reveals that the molar mass of the macromonomer in the hydrophilic shell rather than the mere length is the crucial factor to form an efficiently stabilizing hydrophilic shell. A hydrophilic/lipophilic balance of 0.8 is shown to stabilize unimolecular micelles in water. An extensive in vitro biological evaluation shows neither blood nor cytotoxicity. The applicability of the polymers as drug delivery systems was proven by the encapsulation of the anticancer drug doxorubicin, whose cytotoxic effect was retarded in comparison to the free drug.