Entsar A Saad1, Heba M Waly2. 1. Chemistry Department, Faculty of Science, Damietta University, Damietta, 34517, Egypt. entsarsaad@gmail.com. 2. Chemistry Department, Faculty of Science, Damietta University, Damietta, 34517, Egypt.
Abstract
PURPOSE: Searching for novel anticancer therapeutics which are effective and primarily less toxic is urgently needed. Drug encapsulation provides more protection of drug within the body with more stable drug circulation levels thus avoiding drug peak-related adverse effects. We aimed first to develop and characterize a nano-particulate drug delivery system using poly(lactic-co-glycolic acid) (PLGA) for the new compound N-butylpyridoquinoxaline 1,4-dioxide (NBPQD), and second to investigate its anticancer effect and the probable mechanism. METHODS: NBPQD-PLGA nano-particles were prepared and their shape, size, zeta potential, encapsulation efficiency (EE%), drug loading (DL%), drug release, anticancer activity against six human cancer cell lines, DNA binding ability, and flow cytometric analyses of apoptosis, cell cycle and caspase-3 activity were investigated. RESULTS AND CONCLUSIONS: NBPQD-PLGA nano-particles were spherical with diameter around 54 nm. Zeta potential, EE%, and DL% values were - 20.4 mV, 88% and 21.8%, respectively. Nano-particles exhibited higher marked anticancer activities (much lower IC50s) and changed the anticancer potency pattern towards all the studied cell lines compared to free NBPQD with superior potency against colorectal carcinoma (HCT-116, IC50 of 12.2 µg/mL). NBPQD-PLGA acts by induction of cancer cell apoptosis through oxidative stress, DNA damage, and activating a caspase-3 signaling pathway.
PURPOSE: Searching for novel anticancer therapeutics which are effective and primarily less toxic is urgently needed. Drug encapsulation provides more protection of drug within the body with more stable drug circulation levels thus avoiding drug peak-related adverse effects. We aimed first to develop and characterize a nano-particulate drug delivery system using poly(lactic-co-glycolic acid) (PLGA) for the new compound N-butylpyridoquinoxaline 1,4-dioxide (NBPQD), and second to investigate its anticancer effect and the probable mechanism. METHODS:NBPQD-PLGA nano-particles were prepared and their shape, size, zeta potential, encapsulation efficiency (EE%), drug loading (DL%), drug release, anticancer activity against six humancancer cell lines, DNA binding ability, and flow cytometric analyses of apoptosis, cell cycle and caspase-3 activity were investigated. RESULTS AND CONCLUSIONS:NBPQD-PLGA nano-particles were spherical with diameter around 54 nm. Zeta potential, EE%, and DL% values were - 20.4 mV, 88% and 21.8%, respectively. Nano-particles exhibited higher marked anticancer activities (much lower IC50s) and changed the anticancer potency pattern towards all the studied cell lines compared to free NBPQD with superior potency against colorectal carcinoma (HCT-116, IC50 of 12.2 µg/mL). NBPQD-PLGA acts by induction of cancer cell apoptosis through oxidative stress, DNA damage, and activating a caspase-3 signaling pathway.
Entities:
Keywords:
Anticancer; Caspase-3; Cell cycle; Cytotoxicity; DNA damage; Quinoxaline