Plant-derived extracellular vesicles for itraconazole delivery across the blood-brain barrier for potential glioblastoma treatment

Q: Why is itraconazole delivery to the brain difficult for glioblastoma therapy?

The BBB restricts the transport of therapeutic agents into the brain, reducing the effectiveness of conventional treatments for glioblastoma.

Q: How were plant-derived extracellular vesicles (PDEVs) evaluated in this study?

PDEVs from aloe, ginger, and Nigella sativa seeds were compared for their physicochemical properties, itraconazole release kinetics, cytotoxicity, cellular uptake in glioblastoma cells, and BBB permeability.

Q: Which PDEVs showed BBB permeation in the permeability tests?

Ginger and aloe extracellular vesicles permeated the BBB, whereas blank and loaded EVs from black cumin seeds did not permeate the BBB.

Sep 22, 2026

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Glioblastoma treatment is hindered by the blood-brain barrier (BBB), which restricts therapeutic delivery, while new drug discovery remains limited. This study compares plant-derived extracellular vesicles (PDEVs) isolated from aloe, ginger, and Nigella sativa seeds for physicochemical properties, itraconazole loading and release kinetics, cytotoxicity, cellular uptake in glioblastoma cells, and BBB permeability. All PDEVs were nanoscale with sustained drug release under 50% over 21 days, showing improved viability in non-cancerous cells and better uptake for loaded vesicles.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Background

Results

Physicochemical characterization

Drug release kinetics

Cytotoxicity and cellular uptake

BBB permeability

Conclusions

Future studies

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Plant-derived extracellular vesicles for itraconazole delivery across the blood-brain barrier for potential glioblastoma treatment Naznin Bhom1, Poornima Ramburrun1, Khonzisizwe Somandi1,2 & Yahya E. Choonara1,2􀀍 Background A major challenge in central nervous system disorders such glioblastoma includes the presence of a blood-brain barrier which restricts the delivery of therapeutic agents to the brain, thereby limiting the effectiveness of most conventional treatments. Moreover, the discovery of novel drugs for glioblastoma has been limited hence drug repurposing has gained traction leveraging existing drugs like itraconazole. Plant-derived extracellular vesicles (PDEVs) have potential as a natural pharmaceutical delivery system owing to their therapeutic capabilities. These PDEVs may be a good candidate for blood-brain barrier permeation due to their biomolecular composition and high drug loading efficiency of itraconazole. In this work, PDEVs isolated from aloe aborescens (aloe), Zingiber officinale (ginger) and Nigella sativa seeds [black cumin seeds (BCS)] were compared in terms of their physicochemical properties, drug release kinetics, cytotoxicity, cellular uptake in glioblastoma cells and BBB permeability. Results All PDEVs displayed nanoscale sizes ranging from 103.5 to 141 nm with negative surface charge and a spherical morphological shape observed via SEM. The drug release kinetics was assessed using different mathematical models depicting the PDEVs prolonged drug release with < 50% releasing over 21 days. The cytotoxicity studies showed that the PDEVs resulted in a higher cell viability in the non-cancerous cell line compared toA172 glioblastoma cell line. The cellular internalization of the drug showed poor uptake of blank PDEVs compared to loaded PDEVs in glioblastoma cells. The BBB permeability test showed that ginger and aloe EVs permeated the BBB whilst BCS blank and loaded EVs did not permeate the BBB. Conclusions This delivery system improves the ability of plant-derived extracellular vesicles to cross the blood-brain barrier, addressing a key challenge in delivering treatments to the brain. Through successful encapsulation of itraconazole, itpaves the way for glioblastoma treatment by repurposing itraconazole with improved efficacy and reduced side effects. Furthermore, this can be incorporated in various drug delivery vehicles depending on the route of administration and therapeutic outcome i.e. intranasal, intravenous, or oral route. Future studies focus on determining the composition of PDEVs to enable engineering strategies for next generation targeting via surface modification. Keywords Blood-brain barrier, Plant-derived extracellular vesicles, Glioblastoma, Drug repurposing, Drug delivery, Itraconazole The blood-brain barrier (BBB) constitutes brain endothelial cells surrounded by pericytes, astrocytes, neurons and microglial cells that regulates the permeability of substances moving across the neurovascular region1,2. The BBB interface facilitates the transport of lipophilic molecules (< 400 Da) into the neurovascular region, critically important for advanced drug delivery for brain tumours (Glioblastoma Multiforme – GBM) . While selective permeability of the BBB is essential to maintain brain homeostasis, it is a significant challenge for drug delivery to treat CNS conditions such as GBM. Hence, BBB-targeting delivery systems has become a major focus area of innovation. 1Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown,, Johannesburg 2193, South Africa. 2Wits Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown,, Johannesburg 2193, South Africa. 􀀍 email: [yahya.choonara@wit

FAQs

Why is itraconazole delivery to the brain difficult for glioblastoma therapy?

The BBB restricts the transport of therapeutic agents into the brain, reducing the effectiveness of conventional treatments for glioblastoma.

How were plant-derived extracellular vesicles (PDEVs) evaluated in this study?

PDEVs from aloe, ginger, and Nigella sativa seeds were compared for their physicochemical properties, itraconazole release kinetics, cytotoxicity, cellular uptake in glioblastoma cells, and BBB permeability.

Which PDEVs showed BBB permeation in the permeability tests?

Ginger and aloe extracellular vesicles permeated the BBB, whereas blank and loaded EVs from black cumin seeds did not permeate the BBB.

Sep 22, 2026

Upload by Logic