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    Development of anti-cancer nanoformulations by incorporation of water-insoluble natural bioactive agents into lipid-based drug delivery systems
    (İstanbul Medipol Üniversitesi, Fen Bilimleri Enstitüsü, 2022) Karroum, Reem; Üçışık, Mehmet Hikmet
    Broccoli is a well-known and highly consumed vegetable around the world, it falls into the cruciferous category, which is proven to be effective against breast, skin, and prostate cancers. This anti-cancer property stems from the presence of sulforaphane within the broccoli. In this study, we aim to investigate this cancer chemo-preventive feature by encapsulating sulforaphane within a lipid-based drug delivery system known as emulsomes. We started our experiment by synthesizing blank emulsomes, followed by sulforaphane-emulsomes formulation. The first part of this project contained the characterization techniques which included: zetasizer to investigate the size (246 nm) and the potential (-22.5 mV) of the samples, then microscopy analysis took place, both SEM and CLSM to show the uniformed spherical structure, followed by HPLC quantification studies to obtain the sulforaphane's concentration in the emulsome (288 µM). The focus of the second section was on cell culture research; MCF-7 cell lines were proliferated for three days before being employed for investigations on cell viability. Later, the MTT test was used to conduct the investigations. The results were then examined revealing a 60, 57, and 56% cell viability after the passage of 24, 48, and 72 hours, respectively. To confirm that sulforaphane-emulsome has no harmful effects on healthy epithelial cells, the same process was then applied to the control group of MCF10A healthy cell lines, obtaining 85, 82, and 80% cell viability values after 24, 48, and 72 hours, respectively. To further affirm sulforaphane's anti-cancer effect, apoptosis studies were carried out by performing flow cytometry, which further proved the induction of early apoptosis (~30%) when 10uM of sulforaphane-emulsome was administrated. The obtained data were sufficient to prove the efficacy of sulforaphane-loaded emulsomes, which provided insight for various future ideas and further studies that could be done to investigate the various properties of sulforaphane. For example, it can be tested for its genetic pathway and various effect on different cancer types.
  • Küçük Resim
    Öğe
    Efficacy and safety of sulforaphane-loaded emulsomes as tested on MCF7 and MCF10A cells
    (2024) Karroum, Reem; Üçışık, Mehmet Hikmet
    Objectives: Sulforaphane is well-known for its anti-cancer properties particularly against breast, skin and prostate cancers. High sensitivity of sulforaphane to oxygen, heat, and alkaline conditions, as well as its poor oral bioavailability and water instability limit its use in medicine. In this study, we aim to overcome the prementioned limitations by encapsulating sulforaphane within a lipid-based drug delivery system, known as emulsome, and investigate the anti-cancer features of the attained formulation. Methods: The stability and dispersity of the formulation were assessed sequentially by zeta sizer, scanning electron microscopy and confocal laser scanning microscopy. Cell culture studies were performed to evaluate the anticancer activity of the formulation. Results: Sulforaphane-loaded emulsomes with an average particle size of 246.0±14.1 nm, an average zeta potential of −23.5±2.4 mV and a polydispersity index of around 0.38 were produced. Encapsulations up to 0.036 mg/mL sulforaphane concentration was achieved. When MCF7 breast cancer cells were treated with sulforaphane-loaded emulsomes, a significant decrease was observed in proliferation of the cells along 72 h. In control group, emulsomes were found safe as tested at same concentrations on MCF-10a healthy cells. Applied as dissolved in DMSO, free sulforaphane with an IC50 value of 1.2 µM was more effective against MCF7 cells than sulforaphane-loaded emulsome formulation having a IC50 value 21.1 µM. Conclusions: Sulforaphane-loaded emulsomes were obtained as stable, moderately disperse suspensions. Delivery of the bioactive compound into the cells were achieved. Yet, its biological activity remained behind its free form.