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Corona effects_ChemRxiv_V01.pdf (8.06 MB)
Think Beyond the Core: The Impact of the Hydrophilic Corona on the Drug Solubilization Using Polymer Micelles
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Polymeric micelles are typically characterized as core-shell structures. The hydrophobic inner core is considered as depot for hydrophobic molecules such as drugs or catalysts and the corona forming block acts as protective, stabilizing and solubilizing interface between the hydrophobic core and the external aqueous milieu. Tremendous efforts have been made to tune the hydrophobic block to increase the drug loading and stability of the micelles, while the role of hydrophilic blocks regarding drug loading and stability of micelles is rarely studied in detail. To do so, we investigated a small library of structurally similar A-B-A type amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s by varying the hydrophilic block A utilizing poly(2-methyl-2-oxazoline) (A) or poly(2-ethyl-2-oxazoline) (A*), both excellently water-soluble polymers that are able to provide beneficial stealth properties. Surprisingly, major differences in loading capacities from A-B-A > A*-B-A > A*-B-A* highlight the impact of the hydrophilic corona of the polymer micelles on drug loading and stability. 1H-NMR spectroscopy revealed that the hydrophilic pEtOx exhibits a stronger interaction with the cargo compared with its more hydrophilic counterpart pMeOx, reducing colloidal stability of the drug loaded micelles at lower drug loading. To gain more insights, formulations were also characterized by diffusion ordered and nuclear Overhauser effect NMR spectroscopy, dynamic light scattering and (micro) differential scanning calorimetry. Our findings suggest that the interaction between the hydrophilic block and the guest molecule should be considered an important but previously largely ignored factor for the rational design of polymeric micelles.
M.M.L. and R.L. are listed as inventors on a patent application pertinent to some of the materials discussed in this contribution. R.L. is co-founder and has a financial interest in DelAqua Pharmaceuticals Inc. which is intent on commercializing poly(2-oxazoline) based excipients.