Document Details
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Document Type |
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Thesis |
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Document Title |
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STUDY OF THE ANTIPROLIFERATIVE EFFECT OF ANDROGRAPHOLIDE-LOADED PHYTOSOMES AGAINST LIVER CANCER CELLS دراسة التأثير المضاد للنمو للفايتوسومات المحملة بالأندروجرافولايد ضد خلايا سرطان الكبد |
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Subject |
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Faculty of Science |
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Document Language |
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Arabic |
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Abstract |
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Andrographolide (AG), a main active component of Andrographis paniculata, is known to suppress the proliferation of several types of cancer. However, its use in clinical applications is constrained by its poor pharmacokinetic properties. This study aimed to formulate AG-loaded phytosomes (AG-PTMs) to enhance the antiproliferative activity of AG against hepatocellular carcinoma cell line (HepG2). Methods: The formulation was optimized to achieve minimal particle size, in which L-α-phosphatidylcholine (PC): AG ratio and sonication time (ST) were selected as independent variables. The optimized formulation was characterized by entrapment efficiency, Fourier-transform infrared spectroscopy (FTIR), and an in vitro drug release pattern. After that, the effect of the optimized AG-PTMs on HepG2 cells' proliferation, cellular uptake, cell cycle, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and active caspase-3 protein concentration were evaluated in comparison to raw AG. Furthermore, the mRNA expression of the apoptotic-related genes (BAX, BCL2, and CYCS) and metastatic-related genes (MMP7, MMP9, and CDH2) were also examined. Results: The optimized formula was prepared at 1:2.7 for AG: PC molar ratio and 4.9 min for ST and exhibited a particle size of 243.7 ± 7.3 nm and entrapment efficiency of 72.20 ± 4.53%. FTIR indicated new hydrogen bond formation, indicating the successful formulation of AG-PTMs. Also, the prepared formula showed a slow release of AG over 24-h period. AG-loaded PTMs exhibited a significant improvement in antiproliferative activity against HepG2 cells compared to AG, with half maximal inhibitory concentration (IC50) value of 4.02 ± 0.14 µM and increased cellular uptake of AG. AG-PTMs also caused G2-M cell cycle phase arrest and increased the apoptotic cell fraction. |
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Supervisor |
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Prof. Dr. Osama Abdullah Abuzinadah |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1445 AH
2023 AD |
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Co-Supervisor |
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Dr. Thikryat Abdullatif Neamatallah |
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Added Date |
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Wednesday, December 27, 2023 |
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Researchers
| هوازن هشام مليح | MELAIH, Hawazen Hisham | Researcher | Doctorate | |
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