Developing fully synthetic, non-animal-derived hydrogels for therapeutic applications is a key challenge in clinical biotechnology. Glioblastoma is an aggressive brain cancer with high recurrence rates, needing innovative treatment strategies where the mainstay is surgical removal, and adjuvant radio- and chemotherapy.

This study explores peptide-based hydrogels as drug delivery platforms for Glioblastoma, using Temozolomide (TMZ). We first studied three peptide designs—F8, KF8K, and E2(FKFE)2E— for the encapsulation of TMZ and observed varying release profiles through UV Spectrometry. We found low pH formulation as an important parameter in preserving the TMZ. We also investigated the effect of TMZ precipitation towards the release kinetics, which contributes to a slower release profile. Metabolic activity assay of U251 MG confirmed therapeutic preservation of TMZ, with E2(FKFE)2E surprisingly exhibiting inherent cytotoxicity. F8 had the most promising stabilisation, release and therapeutic preservation of TMZ owing to its low acidic profile. We then studied F8 potential cytotoxicity towards healthy glial cells, which are usually within the surgical site proximity, namely, Human Astrocytes and Microglia, using established cell lines. The peptides do not show any regression in metabolic activity. We found that F8 has the most promising potential for in vivo drug delivery and will be the focus of the next phase of this investigation.