A novel furo[2,3-d]pyrimidine-based chalcone derivative (MMK-1931) loaded chitosomes as a potential cancer therapy in an Ehrlich ascites tumour model.

The pursuit of effective, non-invasive cancer therapies has propelled the development of oral delivery systems capable of overcoming the limitations of conventional chemotherapy. A novel furo[2,3-d]pyrimidine-based chalcone derivative, MMK-1931, was successfully encapsulated into chitosan-coated liposomes (chitosomes) to create an oral anticancer nanomedicine. Both MMK-1931-loaded liposomes and chitosomes were formulated, producing spherical nanoparticles (NPs) with a nanometric size range and high entrapment efficiency. Optimisation studies were conducted to select the most effective formulation. Structural characterisation using FTIR and differential scanning calorimetry (DSC) confirmed drug encapsulation and formulation integrity. In vivo evaluation in an Ehrlich ascites carcinoma (EAC) mouse model demonstrated that MMK-1931-loaded chitosomes (MMK-1931-Chitosomes) significantly suppressed tumour growth, as evidenced by substantial reductions in tumour volume and weight. They also activated apoptotic pathways, as demonstrated by the upregulation of Bax and caspase-9 and the downregulation of Bcl-2. Moreover, they modulated oncogenic signalling by reducing cyclin D and MDM2 levels while enhancing the expression of p53 and PTEN. Histopathological analysis confirmed widespread tumour necrosis and membrane damage. Notably, the antitumor efficacy of orally administered MMK-1931-Chitosomes was comparable to that of intraperitoneally delivered cisplatin, underscoring their potential as a safer, more patient-friendly alternative and establishing them as a promising oral nano-system for solid tumour therapy.