Structure-property relationships in ultra-high loaded API nanoformulation using poly(2-oxazoline)/poly(2-oxazine) amphiphiles

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Polymers are a very important class of pharmaceutical excipients. They can be utilized for controlled release of active pharmaceutical ingredients or to increase their apparent solubility (supersaturation). Polymer micelles are particularly useful to increase the aqueous solubility of water-insoluble drugs and have been investigated to this end intensively. One of the commonly noted limitations of polymer micelles is their limited drug loading and formulation stability. The applicant has investigated for some time a particular polymer platform on the basis of poly(2-oxazoline)s and recently also poly(2-oxazine)s. With these polymers, it was possible to obtain stably drug loaded micelles with an unusually high drug loading (approx. 50 wt.% of dispersed phase) and solubility (increase of drug concentration from approx. 0.001 g/L to approx. 50 g/L). The aim of this project is the elucidation of structure-property relationships between polymer and drug structure on the one hand and the drug loading on the other hand. To this end, we will correlate the drug loading with data on the molecular drug/polymer interactions obtained from infrared, Raman and NMR-spectroscopy. In addition, we will correlate the drug loading with the solubility parameter of the polymers and drugs as well as the polarity of the micellar core. In summary, we expect a detailed understanding of the molecular structure-property relationships which may explain why this polymer platform allows such extraordinary high loading. This, in turn, will allow us the rational design of promising drug-polymer combinations.