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Albumin-Based Drug Delivery for Glioblastoma Treatment: Mechanistic Rationale, Preclinical Evidence, and Clinical Translation

Year: 2026
Type: article
Abstract: Glioblastoma remains the most aggressive primary brain malignancy, with poor survival despite maximal safe resection, radiotherapy, and temozolomide-based chemotherapy. A major obstacle to effective treatment is the spatially heterogeneous blood-brain barrier/blood-tumor barrier, which restricts drug penetration into infiltrative tumor regions and limits uniform intratumoral exposure. Albumin-based delivery is attractive in glioblastoma because it addresses several formulation-level barriers at once: poor aqueous solubility of hydrophobic payloads, short systemic exposure, and the need for a biocompatible carrier that can interact with albumin-handling pathways such as gp60/albondin, SPARC, FcRn, and caveolin-associated transport. This review examines albumin-based strategies explored for glioblastoma, with an emphasis on albumin-bound paclitaxel nanoparticles, engineered albumin nanoparticles, dual-payload systems, albumin-binding photosensitizers, macrophage-assisted delivery, and albumin-bound pathway-directed agents. Preclinical evidence suggests that these platforms can improve brain-tumor drug exposure, support rational combinations, and synergize with BBB/BTB-opening technologies. Early clinical studies combining low-intensity pulsed ultrasound with microbubbles and albumin-bound paclitaxel provide human proof of concept for regional pharmacokinetic enhancement in recurrent glioblastoma, although survival benefit remains unproven. The available evidence supports albumin-based delivery as a rational formulation strategy. Its clinical value in GBM will depend on three testable requirements: spatial pharmacokinetic confirmation, biomarker-guided patient selection, and reproducible BBB/BTB modulation.
Source: Cells
Language: English
Subfield: Biomaterials
Open Access status: gold
Estimated APC paid: $3,258
Award: G186635319
OpenAlex ID: W7166531501
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