ArticleDrug delivery and translational research2025
mPEG-PLA micelles for nose-to-brain delivery of crizotinib-heptamethine cyanine dye conjugate for potential treatment of glioblastoma.
Article in Drug delivery and translational research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Substituent Effects of Heptamethine Cyanine Dyes on Drug Uptake in Patient-Derived Glioma Cells.ChemMedChem · 2026Article
- Imaging of intranasal drug delivery to the brain: updated review 2.0.Drug delivery and translational research · 2026Review
- Nose-to-brain administration of cannabidiol-loaded polymeric micelles improves the core behavioral symptoms of autism spectrum disorder.Bioactive materials · 2026Article
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Authors and funding
11 authors.
Funding
Abstract
Glioblastoma (GBM) is one of the most challenging tumours to treat, with considerable intra- and inter-tumoral heterogeneity and limited treatment options, mainly because of the presence of the blood-brain barrier (BBB). Heptamethine cyanine dyes (HMCDs), such as IR786, have been recently utilised to improve tumour tissue specificity of drugs for treating brain cancers. Their conjugates with drugs such as tyrosine kinase inhibitors (TKIs), which can target multiple pathways aberrantly activated in GBM, provide new avenues for GBM treatment. To improve the therapeutic potential of such drug-dye conjugates and minimise the off-target effects, polymeric micelles prepared using methoxy polyethylene glycol-block-polylactic acid (mPEG-PLA), were developed for encapsulation of a conjugate consisting of ALK inhibitor crizotinib and HMCD IR786 for nose-to-brain (intranasal) delivery. Crizotinib-IR786 micelles were 99.6 ± 9.1 nm in diameter with a zeta potential of 12.8 ± 2.2 mV and average drug loading of 2.9%. On U87MG and KNS42 GBM cell models, crizotinib-IR786 micelles showed comparable cytotoxicity to that of free crizotinib-IR786, and both were significantly more potent than crizotinib alone or crizotinib-only micelles. In a preliminary proof-of-concept trial, the crizotinib-IR786 micelles when administered intranasally to orthotopic GBM mice, demonstrated uptake through the nasal epithelium and accumulated in the GBM tumour, confirming the nose-to-brain delivery pathway. In conclusion, this study demonstrated that the mPEG-PLA micelles can be potentially used as a suitable delivery vehicle for nose-to-brain delivery of crizotinib-IR786 for the treatment of GBM. The promising in vivo preliminary proof-of-concept warrants further detailed in vivo efficacy studies.
Indexed as
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.