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Investigating the Effect of Niosomes Containing Simvastatin on Breast Cancer Cell Line

Akbarzadeh, Iman | 2019

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 52043 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Yaghmaei, Soheila; Bakhshandeh Abkenar, Haleh; Ahangari Cohan, Reza
  7. Abstract:
  8. Breast cancer is the fifth cause of death from cancer and one of the most common fatal cancers in women. The commonly drugs used to treat cancer often destroy healthy tissues and cells and cause common side effects. It is also necessary to consume a large amount of the drug to achieve a particular effect. One of the applications of nanotechnology is drug delivery. Niosomes are one of the newest drug delivery systems that are nowadays much more widely considered due to better penetration and controlled release. One of the most effective medicines for treating breast cancer is statins. These drugs are a group of lipids lowering drugs that lower the synthesis of cholesterol by inhibiting the HMG-COA reductase enzyme. In this study, simvastatin was encapsulated into niosomal nanocarrier by thin film hydration method, as one of the drugs in this category and optimization was performed based on three main characteristics of the nanocarriers, namely, size, particle size distribution (PDI), and entrapment efficiency. According to the designed tests, 0.05 mmol span80 surfactant, with drug to cholesterol ratio (0.4) and sonication time for 7 minutes was selected as the optimal form. The optimal nanoniosomal particles had the size of 168.5 nm, PDI 0.34, and 96.4% entrapment efficiency. nanoniosomes were evaluated in terms of morphological characteristics using transmission electron microscopy and particles showed a single-layer spherical structure. The process of drug release from the nanocarrier was studied. As the hydrophobic nature of the drug and the compact structure of the carrier were expected, the release rate of nanocarrier was slow within 72 hours. At the end of 72 hours, only 18.5% of the drug was released from niosome. The kinetics of drug release from the nanoparticle follows the Higuchi model, which indicates the mechanism of drug diffusion of the carrier. Stability study was carried out on optimal form at two temperatures 25 ° C and 4 ° C for 3 months. stability results indicated that the samples stored at refrigerator had a higher stability than those stored outside in the environment with respect to size, particle size distribution (PDI), and entrapment efficiency. In this study, the effect of simvastatin-niosome nanodrug on the cell line of breast cancer was investigated by MTT and flow cytometry and the effect of nanodrug was studied on expression of bax, bcl2 and p53 genes by Real Time PCR. The results of this study showed that nanodrug had the most cytotoxic effect during 72 hours at concentration of 500 μg / ml compared to other concentrations. flow cytometry studies of Annexin-v-PI showed that cell death, necrosis and apoptosis of MDA / MB231 cells treated with the highest concentrations of nanodrug increased after 72 hours compared to the control group (MDA / MB231 cells without nanodrug). The results of the Real Time PCR method of bax, bcl2 and p53 genes in the treatment group indicated an increase in the expression of these genes as compared to the control group. According to the results, noisome containing simvastatin induces apoptosis of cancer cells, thus, it can be a good candidate for the treatment of breast cancer
  9. Keywords:
  10. Niosome ; Simvastatin ; Breast Cancer ; Apoptosis ; Drug Delivery

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