Issue 24, 2023

Cross-linkable star-hyperbranched unimolecular micelles for the enhancement of the anticancer activity of clotrimazole

Abstract

Clotrimazole, a hydrophobic drug routinely used in the treatment of vaginal candidiasis, also shows antitumor activity. However, its use in chemotherapy has been unsuccessful to date due to its low solubility in aqueous media. In this work, new unimolecular micelles based on polyether star-hyperbranched carriers of clotrimazole are presented that can enhance solubility, and consequently the bioavailability, of clotrimazole in water. The amphiphilic constructs consisting of a hydrophobic poly(n-alkyl epoxide) core and hydrophilic corona of hyperbranched polyglycidol were synthesized in a three-step anionic ring-opening polymerization of epoxy monomers. The synthesis of such copolymers, however, was only possible by incorporating a linker to facilitate the elongation of the hydrophobic core with glycidol. Unimolecular micelles-clotrimazole formulations displayed significantly increased activity against human cervical cancer HeLa cells compared to the free drug, along with a weak effect on the viability of the normal dermal microvascular endothelium cells HMEC1. This selective activity of clotrimazole on cancer cells with little effect on normal cells was a result of the fact that clotrimazole targets the Warburg effect in cancer cells. Flow cytometric analysis revealed that the encapsulated clotrimazole significantly blocks the progression of the HeLa cycle in the G0/G1 phase and induces apoptosis. In addition, the ability of the synthesized amphiphilic constructs to form a dynamic hydrogel was demonstrated. Such a gel facilitates the delivery of drug-loaded single-molecule micelles to the affected area, where they can form a continuous, self-healing layer.

Graphical abstract: Cross-linkable star-hyperbranched unimolecular micelles for the enhancement of the anticancer activity of clotrimazole

Supplementary files

Article information

Article type
Paper
Submitted
01 12月 2022
Accepted
20 2月 2023
First published
21 2月 2023

J. Mater. Chem. B, 2023,11, 5552-5564

Cross-linkable star-hyperbranched unimolecular micelles for the enhancement of the anticancer activity of clotrimazole

M. Gosecki, P. Ziemczonek, M. Gosecka, M. Urbaniak, E. Wielgus, M. Marcinkowska, A. Janaszewska and B. Klajnert-Maculewicz, J. Mater. Chem. B, 2023, 11, 5552 DOI: 10.1039/D2TB02629E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements