Positively Charged Polymers Based on Cyclodextrins for Trametinib and Selumetinib Delivery in Glioblastoma Cancer

TL;DR

Researchers developed positively charged cyclodextrin polymers to improve the delivery of cancer drugs trametinib and selumetinib for treating glioblastoma, a deadly brain tumor.

Contribution

The study introduces cationic cyclodextrin polymers as novel nanocarriers for MEK inhibitors in glioblastoma treatment.

Findings

Cyclodextrin-based polymers enhance drug delivery across the blood-brain barrier.

The polymers improve the antiproliferative effect of trametinib and selumetinib in glioblastoma cells.

Multivalent architecture and positive charge of the polymers facilitate drug encapsulation and cell membrane interactions.

Abstract

Glioblastoma (GB) is the most common and aggressive malignant brain tumor, with a median survival of only 12–15 months despite current treatments with surgery, radiotherapy, and temozolomide (TMZ). Although TMZ induces cytotoxic DNA methylation in tumor cells, its efficacy is often limited by resistance mechanisms. To overcome these limitations, alternative therapeutic strategies—such as targeting the mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK) signaling pathway with MEK inhibitors like trametinib and selumetinib—are being explored. However, their clinical success is currently hindered by inadequate delivery across the blood–brain barrier and dose‐limiting toxicity. Nanoparticles, particularly positively charged systems, offer enhanced cellular uptake and therapeutic performance due to their strong interactions with negatively charged cell membranes. Cyclodextrin (CyD)‐based polymers are promising systems owing to their low toxicity and ability to form inclusion complexes with drugs. In this work, we investigate two cationic CyD polymers as potential nanocarriers for GB therapy based on trametinib and selumetinib. Their multivalent architecture and positive charge can facilitate both the encapsulation of drugs and membrane interactions. These systems present promising candidates for enhancing the efficacy of GB treatment.

β‐cyclodextrin‐based multicharged polymers—linear or cross‐linked—enhance the delivery of mitogen‐activated protein kinase inhibitors (selumetinib, trametinib) in glioblastoma cells. These carriers enhance the antiproliferative effect of the drugs and strengthen extracellular signal‐regulated kinase pathway inhibition.© 2026 WILEY‐VCH GmbH

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