Polyesteramide Nanoparticles with “stealth polymer” shell
Michael Dirauf, Irina Muljajew, Christine Weber, Ulrich S. Schubert*
Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstr. 10, 07743 Jena, Germany
Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany
Nanoparticle mediated drug delivery represents a valuable strategy to enlarge the bioavailability of hydrophobic or sensitive actives. Mostly, biocompatible hydrophobic polyesters are applied for this purpose, as they slowly undergo biodegradation via hydrolysis in presence of esterases or lipases. However, acidic products are formed, limiting the carrier materials to drugs that are stable under acidic conditions. Polyesteramides (PEAs) represent an alternative class of biodegradable polymers, which feature stable amide bonds alongside hydrolysis sensitive ester bonds, making their degradation behavior highly interesting, because less acidic degradation products should be formed.
PEAs are similar accessible by ring-opening polymerization of morpholine-2,5-diones. These were obtained from the natural L-amino acids, glycine, alanine, valine, leucine and isoleucine, enabling access to PEAs with tailored hydrophilicity. Therefore, a controlled ROP utilizing 1,5,7-triazabicyclo[4.4.0]dec-5-ene as an organocatalyst in tetrahydrofuran at room temperature was employed, yielding well-defined PEAs with defined end groups. Stable spherical nanoparticles were obtained via nanoprecipitation. To obtain nanoparticles containing poly(2-ethyl-2-oxazoline) (PEtOx) as “stealth polymer”, a ω-hydroxyl functionalized PEtOx, was utilized as macroinitiator for the ROP of the morpholine-2,5-diones. A library of POx-b-PEA block copolymers was obtained, keeping the degree of polymerization (DP) of the POx constant as 20, while the PEA block was varied in the range of 20 to 100. The resulting block copolymers self-assembled in aqueous media forming various structures. Depending on the block length ratio, micelles, vesicles and nanoparticles were obtained.
 M. Dirauf, D. Bandelli, C. Weber, H. Görls, M. Gottschaldt, U. S. Schubert, Macromol. Rapid Commun. 2018, doi.org/10.1002/marc.201800433.