Structure-Property Relations for Drug Loaded Polymer Micelles using Detailed Structural Information from Solid-State NMR Spectroscopy and Complementary Techniques

• Applicant: Professorin Dr. Ann-Christin Pöppler
• Subject Area: Polymer Materials ; Analytical Chemistry
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 440955393

In a recent proof-of-concept study characterizing ultra-high loaded poly(2-oxazoline) polymer micelles for drug delivery applications, we were able to obtain fascinating insights into the loading dependent assembly of both polymer and guest. Freeze-dried samples were analysed using solid-state NMR spectroscopy complemented by powder X-ray diffraction and quantum chemical calculations. Thereby, it was possible to explain bulk physicochemical properties such as dissolution rates and a set of hypotheses was obtained, for example, that ultra-high drug loadings as observed for these poly(2-oxazoline)s triblock copolymers are only possible if both, the hydrophobic and hydrophilic polymer parts, are involved in the coordination of the encapsulated molecules and thus the stabilization of the micelle. Furthermore, key intermolecular interactions between the polymer and the encapsulated molecules could be identified. Now it is important to address these hypotheses systematically and improve our structural understanding in order to understand the influence of the structure on the drug delivery properties. In a first step, the NMR spectroscopic toolbox for the analysis of such systems will be filled with additional, more sophisticated experiments at moderate to fast magic angle spinning (24-60 kHz) to build a strong basis for the subsequent investigations. A particular focus will be on the use of additional NMR-active nuclei and proton detected solid-state NMR experiments. With this toolbox, we aim at scrutinizing the influence of the structure of the guest molecule as well as of the polymer on the final formulation and expand the investigation to polymers with more functionalities for additional intermolecular interactions. With such optimized formulations, it is then necessary to close the circle by looking at bulk physicochemical properties and the behaviour of the different formulations in biorelevant media to derive structure-property relations. Combined with the valuable improved structural understanding, it will then be possible to initiate a rethinking to use rational design criteria and guidelines for the development of new formulations rather than trial and error approaches as has been mainly done so far. This will make it possible to reason specific polymer modifications and thus boost the transport and uptake of the resulting formulations, ultimately ensuring benefits for the patients.

• DFG Programme: Research Grants