Think Beyond the Core: Impact of the Hydrophilic Corona on Drug Solubilization Using Polymer Micelles
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Abstract
Polymeric micelles are typically characterized as core-shell structures. The hydrophobic core is considered as a depot for hydrophobic molecules, and the corona-forming block acts as a stabilizing and solubilizing interface between the core and aqueous milieu. Tremendous efforts have been made to tune the hydrophobic block to increase the drug loading and stability of micelles, whereas the role of hydrophilic blocks is rarely investigated in this context, with poly(ethylene glycol) (PEG) being the gold standard of hydrophilic polymers. To better understand the role of the hydrophilic corona, a small library of structurally similar A-B-A-type amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s is investigated by varying the hydrophilic block A utilizing poly(2-methyl-2-oxazoline) (pMeOx; A) or poly(2-ethyl-2-oxazoline) (pEtOx; A*). In terms of hydrophilicity, both polymers closely resemble PEG. The more hydrophobic block B bears either a poly(2-oxazoline) and poly(2-oxazine) backbone with C3 (propyl) and C4 (butyl) side chains. Surprisingly, major differences in loading capacities from A-B-A > A*-B-A > A*-B-A* is observed for the formulation with two poorly water-soluble compounds, curcumin and paclitaxel, highlighting the importance of the hydrophilic corona of polymer micelles used for drug formulation. The formulations are also characterized by various nuclear magnetic resonance spectroscopy methods, dynamic light scattering, cryogenic transmission electron microscopy, 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.
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PMeOx is more hydrophilic than PEG, is well-hydrated in the shell of highly drug-loaded POx micelles, and interacts less with loaded drug than PEtOx.
“For example, PMeOx (which is more hydrophilic than PEG) was well-hydrated in the shell of highly drug-loaded POx micelles and had less interaction with loaded drug compared to PEtOx (which is similarly hydrophilic to PEG).”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [119]
The high loading capacity of poorly soluble drugs in POx micelles is due to the structure of both hydrophilic and hydrophobic blocks in POx triblock copolymers.
“Interestingly, it was recently reported that such high loading capacity of poorly soluble drugs in POx micelle was due to the structure of both the hydrophilic and hydrophobic blocks in POx triblock copolymers [119].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [119]
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- Authors
- Haider, M. S., Lübtow, M. M., Endres, S., Forster, S., Flegler, V. J., Böttcher, B., Aseyev, V., Pöppler, A.-C., & Luxenhofer, R.
- Affiliations
- University of Würzburg (DE)
- Functional Polymer Materials, Chair for Chemical Technology of Material Synthesis and Bavarian Polymer Institute, Faculty of Chemistry and Pharmacy, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany
- University of Helsinki (FI)
- Corresponding author
- Luxenhofer, Robert
- ORCID
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-05-07
- Volume
- 12
- Issue
- 22
- Pages
- 24531-24543
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W3021349866
- Cited by
- 100
- References
- 71
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 14 · 2023: 13 · 2022: 16 · 2021: 18 · 2020: 8
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- Royal College of Surgeons in Ireland (submittedVersion, cc-by-nc-nd)
- Funders
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft (398461692)
- Higher Education Commission, Pakistan
- Verband der Chemischen Industrie
- Evonik Stiftung
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Chemistry › Organic Chemistry › Surfactants and Colloidal Systems
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Keywords
- polymeric micelles, drug solubilization, amphiphilic block copolymers, poly(2-oxazoline), poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), drug loading capacity, curcumin, paclitaxel, core-shell micelles, micelle stability, drug-micelle interaction
- MeSH terms
- Curcumin, Drug Carriers, Drug Compounding, Micelles, Oxazoles, Polymers, Solubility, Surface-Active Agents, Molecular Structure, Paclitaxel, Small Molecule Libraries, Hydrophobic and Hydrophilic Interactions
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