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. Optimization studies were conducted to select the most effective formulation. Structural characterization using FTIR and 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 tumor growth, as evidenced by substantial reductions in tumor 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 signaling by reducing cyclin D and MDM2 levels while enhancing the expression of p53 and PTEN. Histopathological analysis confirmed widespread tumor 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 tumor therapy.