Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using H-NMR, C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The result suggested that DLMF has high therapeutic effectiveness against HCC. pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose's targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an study of DL on caspase 3 and 9 proteins, and the results were found to be -6.7 kcal/mol and -6.6 kcal/mol, respectively. Our analysis revealed that the DL had strong apoptotic properties against HCC.
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http://dx.doi.org/10.3389/fphar.2022.1021867 | DOI Listing |
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Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal, RN, Brazil. Electronic address:
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Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul, Turkiye.
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Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11491, Saudi Arabia.
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December 2024
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
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