طراحي و ارزيابي سامانه دارورساني ميتومايسين و كرايسين بر پايه نانوليپوزوم هاي پاسخگو به pH براي درمان سرطان پستان

Design and eva‎luation of mitomycin and chrysin drug delivery system based on pH-responsive nanoliposomes for breast cancer treatment

مهندسي پزشكي

Cancer is one of the main causes of death and breast cancer is one of the most common types of cancer. Current treatment methods often lack optimal efficacy due to the emergence of drug resistance, low efficacy, and serious side effects. Targeted drug release systems have been proposed as a promising approach to deal with these challenges. The aim of this research is to fabricate, characterize and eva‎luate pH-responsive nanoliposomes loaded with mitomycin and chrysin drugs to treat breast cancer and help the survival of healthy cells and being more lethal for cancer cells. For this purpose, cholesterol (Chol)-phosphatidylcholine (PC) nanoliposomes were made using the thin layer hydration method. The morphology of nanoparticles was investigated by TEM and particle size distribution and zeta potential by DLS and the results showed a large number of completely spherical nanoparticles with a diameter of 90 nm and a surface charge of -27-30 mV. DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine) substance was added to other primary compounds in molar ratios of 0.5, 1, 1.5, 2 and 2.5 in order to create pH response properties. The loading and release of drugs was investigated by spectrophotometry for each of the ratios at different values of pH 4.7 and 5.4, and the optimal amount of DOPE was determined based on the results. The chemical composition of nanoliposomes was checked by FTIR and this eva‎luation showed that their chemical composition is consistent with the raw materials used and there is no new composition in their structure. Mitomycin C and chrysin in five weight ratios of 100:0, 75:25, 50:50, 25:75 and 0:100 were loaded on nanoliposomes and MTT test was used to check the lethality of them on cells include Human venous endothelial (HUVEC), as a normal cell line, and human mammary gland epithelial cells (MCF-7), as a cancer cell line, for 1, 2 and 3 daysʹ cell culture, and among the five ratios Under investigation, the optimal ratio of mitomycin C and chrysin was selected. The results obtained from the optimization of nanoliposomes showed that by adding DOPE compound to the amount of 2 molar ratio to other nanoliposome components, not only the biggest difference between the drug release was obtained in the two tested pHs, but also the drug loading rate was satisfactory in this formulation. The observed significant death of MCF-7 cells in cell culture tests on the second and third day in the presence of chrysin and mitomycin C also indicates the synergy of the antitumor effects of these two agents. The results obtained from HUVEC cell culture also indicated that with the presence of 75% chrysin versus 25% mitomycin, the cell survival process in three consecutive days was nearly 3 times more than the samples with less chrysin content. Despite the high survival rate of 80% of this sample on the first and second day, the reason for the drop in survival rate to 51% on the third day was the complete release of mitomycin and its effect on endothelial cells. Nevertheless, the positive effect of the presence and release of chrysin in the formulation on HUVEC cells is clearly evident. According to the obtained results, Chol-DOPE-PC nanoliposomes loaded with chrysin and mitomycin C can be introduced as a suitable candidate for breast cancer treatment.

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ژاله ورشوساز

مينا ميريان و محمد رفيعي نيا