Impact of the hydrophilic corona on the performance of block copolymer micelles as drug carriers
Anna-Lena Ziegler1, Liliia Simagina1, Ekaterina Takmakova1 and Robert Luxenhofer1
1Department of Chemistry, University of Helsinki, 00014 Helsinki, Finland
Recently, the hydrophilic corona of block copolymer micelles (BCMs) was shown to be of underappreciated importance for drug formulation.[1-2] More precisely, critical but previously ignored corona-drug interactions were demonstrated.[3-4]
Here, we introduce a small library of ABA-type triblocks with varying hydrophilic blocks for systematic investigations regarding the influence of the hydrophilic corona on the performance of BCMs as drug carriers. The synthesis of the copolymers was realized using a polymer-polymer coupling procedure based on copper-catalyzed azide-alkyne cycloaddition reaction.[5] As a central hydrophobic block, poly(2-butyl-2-oxazine) (PBuOzi) was used in all copolymers. For the flanking hydrophilic blocks, a set of well-studied stealth polymers was chosen including poly(2-methyl-2-oxazoline) (PMeOx), poly(N,N-dimethyl acrylamide) (PDMA), polysarcosine (PSar) and the gold standard polyethylene glycol (PEG), among others.
We tested the synthesized copolymers for their loading capabilities of the model drugs curcumin and indomethacin. In this respect, the variation of hydrophilic moieties was shown to have a notable impact on drug solubilization and formulation stability, corroborating previous, less extensive work. Further, we investigated a small selection of polymers for their interactions with the simulated intestinal fluid by 1H NMR shift analysis and diffusion ordered spectroscopy (DOSY) NMR measurements. The analysis revealed only minor differences in their interference with biorelevant media. Lastly, first in vitro endocytosis data of curcumin formulations are obtained to unravel the impact of the hydrophilic corona on cell internalization.
References
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5. Ziegler, A.-L.; Kerr, A.; Kaps, F. T.; Luxenhofer, R.; Triblock architecture and PEG hydrophilic blocks enable efficient thermogelation of poly(2-phenyl-2-oxazine)-based worm-gels. ChemRxiv 2024. This content is a preprint and has not been peer-reviewed. DOI: 10.26434/chemrxiv-2024-75cb8.