More Is Sometimes Less: Curcumin and Paclitaxel Formulations Using Poly(2‐oxazoline) and Poly(2‐oxazine)‐Based Amphiphiles Bearing Linear and Branched C9 Side Chains

• Published in: Macromolecular bioscience Vol. 18; no. 11; pp. e1800155 - n/a
• Main Authors: Lübtow, Michael M., Keßler, Larissa, Appelt‐Menzel, Antje, Lorson, Thomas, Gangloff, Niklas, Kirsch, Marius, Dahms, Selma, Luxenhofer, Robert
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.11.2018
• Subjects: Bearing strength; Block copolymers; Cells, Cultured; Chain branching; Copolymers; Core making; Curcumin; Curcumin - chemistry; Curcumin - pharmacokinetics; Curcumin - pharmacology; drug delivery; Fibroblasts - cytology; Fibroblasts - metabolism; Formulations; Humans; Hydrophobicity; Micelles; nanoformulations; Oxazine; Oxazoles - chemistry; Paclitaxel; Paclitaxel - chemistry; Paclitaxel - pharmacokinetics; Paclitaxel - pharmacology; Polymers; Polyoxazolines; Solubility; Solubilization; structure–property relationships; paclitaxel; drug delivery; nanoformulations; curcumin; structure-property relationships
• ISSN: 1616-5187; 1616-5195; 1616-5195
• DOI: 10.1002/mabi.201800155

A known limitation of polymer micelles for the formulation of hydrophobic drugs is their low loading capacity (LC), which rarely exceeds 20 wt%. One general strategy to overcome this limitation is to increase the amphiphilic contrast, that is, to make the hydrophobic core of the micelles more hydrophobic. However, in the case of poly(2‐oxazoline) (POx)‐based amphiphilic triblock copolymers, a minimal amphiphilic contrast was reported to be beneficial. Here, this subject is revisited in more detail using long hydrophobic side chains that are either linear (nonyl) or branched (3‐ethylheptyl). Two different backbones within the hydrophobic block are investigated, in particular POx and poly(2‐oxazine) (POzi), for the solubilization and co‐solubilization of the two highly water insoluble compounds, curcumin and paclitaxel. Even though high loading capacities can be achieved for curcumin using POzi‐based triblock copolymers, the solubilization capacity of all investigated polymers with longer side chains is significantly lower compared to POx and poly(2‐oxazine)s with shorter side chains. Although the even lower LC for paclitaxel can be somehow improved by co‐formulating curcumin, this study corroborates that in the case of POx and POzi‐based polymer micelles, an increased amphiphilic contrast leads to less drug solubilization. Poly(2‐oxazoline)s and poly(2‐oxazine)‐based amphiphiles have been shown capable of solubilizing extraordinary amounts of hydrophobic drugs within polymer micelles. However, this reportedly works better for polymer micelles with a less hydrophobic core. Here, this issue is reinvestigated, and polymer micelles with a variety of very hydrophobic cores are prepared and investigated thoroughly with respect to their physicochemical properties and solubilization capacity for curcumin and paclitaxel.