Hydrophobic ion pairing enables co-loading of water-soluble drugs in polymeric micelles
Polymeric micelles are widely used for the delivery of hydrophobic drugs. However, several highly potent and ubiquitously used anticancer drugs are water-soluble, complicating their (co-)formulation in polymeric micelles without having to chemically modify them. We here explore hydrophobic ion pairing to enable the co-delivery of the water-soluble anthracycline chemotherapy drug doxorubicin and the angiotensin II receptor antagonist telmisartan (a clinically used antihypertensive drug that has shown promising (pre-) clinical outcomes in combination with anthracyclines). We show that hydrophobic ion pairing of doxorubicin and telmisartan promotes the co-encapsulation of both drugs in π electron-stabilized [PEG-b-p(HPMAm-Bz)]-based polymeric micelles. The cytotoxic activity of doxorubicin is retained, and the dual drug-loaded micelles display enhanced antitumor activity in vivo as compared to the combination of the free drugs, while also exhibiting good tolerability. Taken together, this work provides proof-of-concept for hydrophobic ion pairing as a promising formulation strategy to promote multidrug nanomedicine and drug combination therapy.
Authors
- Quim Peña (ORCID: https://orcid.org/0000-0001-6477-8127)
- Eva Miriam Buhl (ORCID: https://orcid.org/0000-0003-0627-9228)
- Srinivas Banala (ORCID: https://orcid.org/0000-0003-3562-377X)
- Alexandros Marios Sofias (ORCID: https://orcid.org/0000-0002-7475-2526)
- Tarun Ojha (ORCID: https://orcid.org/0000-0002-6038-4558)
- Yang Shi (ORCID: https://orcid.org/0000-0003-4530-2056)
- Alina Adams (ORCID: https://orcid.org/0000-0002-0892-6399)
- Fabian M. Kiessling (ORCID: https://orcid.org/0000-0002-7341-0399)
- Diana Moeckel
- Josbert M. Metselaar
- Asmaa Said Elshafei
- Rasika Daware (ORCID: https://orcid.org/0000-0003-3343-6567)
- Peter Boor (ORCID: https://orcid.org/0000-0001-9921-4284)
- Federica De Lorenzi (ORCID: https://orcid.org/0000-0001-6809-0370)
- Barbara M. Klinkhammer (ORCID: https://orcid.org/0000-0002-1566-7129)
- Twan Lammers (ORCID: https://orcid.org/0000-0002-1090-6805)
- Armin Azadkhah Shalmani (ORCID: https://orcid.org/0000-0003-2238-6525)
- Gert Storm
Institutions
- National University of Singapore (SG)
- Utrecht University (NL)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Journal of Controlled Release
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1016/j.jconrel.2025.113748
- Citations
- 3
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 1.79
Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- H2020 European Research Council
- HORIZON EUROPE European Research Council