# Advancements in Drug Delivery Systems in Glioblastoma Therapy

## TL;DR

This review explores new drug delivery systems for glioblastoma, focusing on overcoming the blood-brain barrier and improving treatment outcomes.

## Contribution

The paper highlights novel drug delivery platforms and strategies for addressing challenges in glioblastoma therapy.

## Key findings

- Nanoparticles and other systems show improved BBB penetration and tumour targeting in preclinical studies.
- Translational challenges include large-scale production and off-target effects.
- Future strategies integrate tumour stress responses into drug delivery design.

## Abstract

Glioblastoma (GB) is one of the most aggressive brain tumours, with a high mortality rate. Tumour heterogeneity, GB’s invasive nature, the blood–brain barrier (BBB) and resistance development offer significant challenges in devising an effective strategy to manage GB. Clinicians rely on tumour resection, radiotherapy and temozolomide (TMZ) chemotherapy, but their efficacy is hindered due to poor BBB penetration. EGFR (epidermal growth factor receptor), NF-κB, angiogenic pathways, RAS/RAF/MAPK, PI3K/Akt/mTOR, etc., play an important role in GB progression. Development in nanotechnology, pharmaceutical science and genetic engineering enables the design of drug candidates with superior efficacy and safety profiles. This review delves into recent advancements in nanoparticles, hydrogels, extracellular vesicles, microneedles and other drug delivery platforms used in GB treatment. These novel drug delivery systems achieved superior BBB penetration, tumour targeting, and controlled release and better survival outcomes in preclinical setups. This review also discusses the major translational challenges, including those of large-scale production, tumour heterogeneity, off-target effects and M2 macrophage induction. Innovative strategies focusing on drug delivery as a biological decision-making process, integrating tumour stress responses into drug carrier and system-level design principles, are discussed, outlining future prospects.