Hydrophobic ion pairing enables co-loading of water-soluble drugs in polymeric micelles

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release Pub Date : 2025-04-17 DOI:10.1016/j.jconrel.2025.113748

Armin Azadkhah Shalmani, Rasika Daware, Asmaa Said Elshafei, Federica De Lorenzi, Diana Moeckel, Eva M. Buhl, Barbara Mara Klinkhammer, Peter Boor, Srinivas Banala, Alina Adams, Fabian Kiessling, Gert Storm, Josbert M. Metselaar, Alexandros Marios Sofias, Yang Shi, Twan Lammers, Quim Peña, Tarun Ojha

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引用次数: 0

Abstract

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.

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.