چكيده به لاتين
Breast cancer is the most common and biggest threat to women's health. There is an urgent need to develop new breast cancer treatments to overcome the shortcomings of conventional chemotherapy and surgery, which include poor drug efficacy, damage to normal tissues, and increased side effects. Drug delivery systems based on nanotechnology have recently attracted a lot of attention, because they provide solutions for localized, targeted and controlled release of drugs to the tumor site. Such systems have great potential to improve drug efficiency and reduce side effects caused by long-term exposure to chemotherapy. Niosomes are a non-toxic and non-immunogenic nanoparticle delivery system that is widely used for drug delivery. Niosomes have gained popularity as a nanocarrier due to their low cost and ease of fabrication. Cyclophosphamide is one of the most common drugs used to treat breast cancer, however, its clinical use is severely limited due to its serious adverse effect. Cyclophosphamide toxicity is mainly the result of oxidative stress caused by an imbalance between reactive oxygen species of antioxidants and also involves multiple signaling pathways. Curcumin is a natural lipophilic polyphenol that exhibits significant pharmacological effects in laboratory and in vivo conditions through different mechanisms. Curcumin is a plant compound obtained from turmeric. Curcumin administration reduces ROS levels to prevent apoptosis in normal cells. The most known molecular targets affected by curcumin for disease treatment are transcription factors, protein kinases, inflammatory mediators and enzymes. Here, the aim of this study is to show the effectiveness of curcumin in reducing the adverse effects of cyclophosphamide and improving its antitumor activity. In this study, cyclophosphamide and curcumin were entrapped in niosomal nanocarriers by thin layer hydration method and optimization was done based on three main characteristics of nanocarriers, i.e. dispersion size, particle size and drug retention efficiency. According to the designed tests, 60 Span surfactant with 5 M drug amount, 58 mg of cholesterol and 33.50 mg was selected as the optimal form. Nanonisomes with an optimized size of 34 nm showed a particle dispersion index (PDI) of 0.14 and a retention efficiency of 99%. The nanoniosomes were evaluated in terms of morphological characteristics using a transmission electron microscope and the particles showed a single-layer spherical structure. The process of release The drug was checked from the nanocarrier during 168 hours. The results showed that at the end of 168 hours, 98.9% and 97.7% of the drugs were released from niosomes containing two drugs, pegylated and folic acid, for cyclophosphamide and curcumin, respectively. Stability studies were carried out during 2 months in two Temperatures of 25° C and 4° C were performed on the optimal sample. The stability results showed that the samples kept in the refrigerator were more stable than the samples kept in the outside environment in terms of the characteristics of dispersion size, particle size and drug retention efficiency. In this research, the effect of niosomal nanocarriers containing two drugs, niosomal nanocarriers containing two pegylated drugs, and niosomal nanocarriers containing two pegylated drugs and folic acid on breast cancer cell lines was performed by the MTT method and observed at concentrations of 25 to 500 micrograms/ml. The survival percentage of cells in the vicinity of Niosomal nanocarriers containing two pegylated drugs and folic acid is lower than in the vicinity of Niosomal nanocarriers containing two pegylated drugs.