A novel strategy for brain cancer treatment through a multiple emulsion system for simultaneous therapeutics delivery

Abstract The research integrates chemical engineering principles with biological insights to overcome key barriers in glioblastoma multiforme (GBM) therapy. GBM remains one of the most aggressive and lethal brain tumours, characterised by its infiltrative growth, chemoresistance and poor prognosis. Conventional chemotherapy faces critical limitations, including restricted drug penetration across the blood–brain barrier, systemic toxicity and tumour resistance to classic treatment. Addressing these challenges, this study proposes an innovative, multiple emulsion–based drug delivery system designed to enhance the therapeutic effectiveness of GBM treatment through synergistic combinations of RNA-class molecules and chemotherapeutic agent (doxorubicin–DOX). The system utilises a pH-responsive biopolymer (carboxymethylcellulose sodium salt), facilitating controlled and selective drug release in the acidic microenvironment of tumour cells (pH 6.3), while preserving healthy tissues. The emulsion structures prepared using Couette–Taylor flow techniques, achieved high encapsulation efficiency of DOX, stability and precise control over release kinetics. The addition of siRNA targets the genetic pathways of tumour DNA repair, sensitising cancer cells to DOX and significantly reducing their viability. Experimental results demonstrated a substantial improvement in cytotoxic efficacy, with up to a 65 % reduction in cancer cell viability compared to conventional DOX solution, further amplified to about 81 % when combined with liposomal siRNA. A mathematical model of drug diffusion and chemical reaction expressing absorption by cancer cells highlights the systems’ potential for personalising therapy by optimising drug dose and release profiles. This approach not only minimises systemic side effects but also provides a platform for targeted, efficient and more patient-friendly cancer treatment. This study establishes multiple emulsion as a promising carrier for dual-drug delivery system, bridging the gap between biological complexity and engineering precision. Future work will focus on in vivo evaluation and clinical validation to realise the potential of this approach in improving GBM patient outcomes.