{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:54:21Z","timestamp":1790351661821,"version":"4.1.0"},"reference-count":230,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Silesian University of Medicine","award":["BNW-1-036\/N\/5\/K"],"award-info":[{"award-number":["BNW-1-036\/N\/5\/K"]}]},{"name":"Silesian University of Technology","award":["32\/007\/RGJ26\/0084"],"award-info":[{"award-number":["32\/007\/RGJ26\/0084"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glioblastoma (GB) is one of the most aggressive brain tumours, with a high mortality rate. Tumour heterogeneity, GB\u2019s invasive nature, the blood\u2013brain 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-\u03baB, 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.<\/jats:p>","DOI":"10.3390\/ijms27052298","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:39:56Z","timestamp":1772455196000},"page":"2298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Advancements in Drug Delivery Systems in Glioblastoma Therapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-9239","authenticated-orcid":false,"given":"Purusottam","family":"Mishra","sequence":"first","affiliation":[{"name":"Biotechnology Center, Silesian University of Technology, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun 248002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6678-8083","authenticated-orcid":false,"given":"Aleksandra","family":"Markowska","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-508X","authenticated-orcid":false,"given":"Saeid","family":"Ghavami","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T6, Canada"},{"name":"Paul Albrechtsen Research Institute, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada"},{"name":"Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Faculty of Medicine, Akademia \u015al\u0105ska, Ul Rolna, 43, 40-555 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3416-7354","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Markowski","sequence":"additional","affiliation":[{"name":"Department of Laryngology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-027 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9518-1411","authenticated-orcid":false,"given":"Marek J.","family":"\u0141os","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Silesian University of Technology, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167653","DOI":"10.1016\/j.bbadis.2024.167653","article-title":"Modern insights of nanotheranostics in the glioblastoma: An updated review","volume":"1871","author":"Sangubotla","year":"2025","journal-title":"Biochim. 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