IN-VIVO ANALYSIS ON XENOGRAFT MICE MODEL AND RELEASE OF CYTARABINE FROM CASEIN COATED IRON OXIDE NANOSTRUCTURE FOR CANCER TREATMENT BY MAGNETIC DRUG TARGETING

Abstract

Cancer is a group of diseases involving abnormal cell growth with the potential to spread to other parts of the body. Chemotherapy is a type of cancer treatment that uses drugs to destroy cancer cells. Thus realizing the need to overcome complexities involved in treating complex diseases motivated the author to design casein coated iron oxide nanoparticles (CCIONPs) crosslinked with glutaraldehyde for achieving efficient MDT. Method: - In order to design casein nanoparticles (CCIONPs) the microemulsion method was adopted and for impregnation of iron oxide nanoparticles into the bulk of casein matrix an in situ co precipitation method was used. In order to characterize nanoparticles FTIR, TEM, VSM, Mossbauer, zeta potential, in-vitro cytotoxicity test were studied on normal cells as well as cancerous cell lines. The nanoparticles were loaded with cytarabine and its controlled release was investigated drug loading, chemical architecture of the nanocarriers, and nature of release media. In vivo analysis was perfomed on mice model and different cell lines.  Results: - FTIR analysis confirmed homogenous deposition of iron oxide and subsequent formation of CCIONPs. The drug loading efficiency of CCIONPs, drug content and in vitro drug release profiles may be measured by ultraviolet spectrophotometer at λ_max 254. It was found to have better payload, in vitro release profile characteristic and better targeting to RES organs. Conclusion: - Glutaraldehyde crosslinked casein coated iron oxide nanoparticles CCIONPs form a swelling controlled drug release system. Cyt loaded CCIONPs successfully inhibited cell cycleprogression and displayed good apoptosis in A549 cells and significantly induced caspase-3 activation and suppressed NF-kB and IL-6 activation in immunocytochemistry, qPCR and western blot analysis. Additionally,  Cyt loaded CCIONPs prominently displayed tumoricidal effects in lung adenocarcinoma in vivo xenograft nude mice model. Thus, the prepared nanoparticles showed potential to provide a possible option for magnetically targeted delivery of anticancer drugs.