El‑Didamony, Samia EAmer, Reham IEl‑Osaily, Ghada H2022-08-052022-08-052022-07https://doi.org/10.1038/s41598-022-17391-whttp://repository.msa.edu.eg/xmlui/handle/123456789/5072Bee venom (B.V.) is a toxin produced naturally by honey bees with several toxic and therapeutic efcacies. It is used in the treatment of diferent cancer kinds like renal, hepatic, and prostate cancer. Due to its protein nature, it is degraded in the upper gastrointestinal tract. Colon-targeted drug delivery systems represent a useful tool to protect B.V. from degradation and can be administered orally instead of I.V. infusion and traditional bee stinging. In the present study, B.V. loaded enteric- coated cross-linked microspheres were prepared by emulsion cross-linking method. Percentage yield, entrapment efciency %, swelling degree, and in-vitro release are evaluated for prepared microspheres. Free B.V., optimized microspheres formula (F3), and doxorubicin cytotoxic efects were tested by MTT assay. Results concluded that free B.V. was more efective against the growth of human prostate adenocarcinoma (PC3) cells followed by optimized microspheres than doxorubicin. But both free B.V. and doxorubicin have a cytotoxic efect on normal oral epithelial cells (OEC). According to fow cytometric analysis, the optimized microsphere formula induced apoptosis and reduced necrosis percent at IC50 concentration. Furthermore, microspheres did not afect the viability of OEC. These results revealed that microspheres have a degree of specifcity for malignant cells. Therefore, it seems that this targeted formulation could be a good candidate for future clinical trials for cancer therapy.en-UScellulartoxicitybee-venommicrosphereCancerArticlehttps://doi.org/10.1038/s41598-022-17391-w