Encapsulation of a new quinoxaline derivative in PLGA alters the pattern of its anticancer potency and induces apoptosis
- 37 Downloads
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.
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.
KeywordsQuinoxaline Cytotoxicity DNA damage Cell cycle Caspase-3 Anticancer
Authors would like to thank Prof. Salem A. Habib and Prof. Mohamed A. Waly, Chemistry Department, Faculty of Science, Damietta University, Egypt, for their valuable help.
Compliance with ethical standards
Conflict of interest
Author Entsar A. Saad declares that she has no conflict of interest. Author Heba M. Waly declares that she has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 9.Al-Mutairi FM, Abdel-Daim MM, Ibrahim IT, Habib SA, Waly HM (2016) The potent effect of a newly synthesized N-Butylpyridoquinoxaline 1,4-dioxide (NBPQD) derivative as antitumor agent in solid tumor model. Int J Pharm Res Allied Sci 5:203–218Google Scholar
- 10.Habib SA, Ibrahim IT, Abd-Eldaye MA, El-Sheshtawey MM, Waly HM (2012) N-Butylpyridoquinoxaline 1,4-dioxide (NBPQD) as a new potent for tumor imaging and therapy. Nat Sci 4:1074–1084Google Scholar
- 16.Chuan L, Jia Z, Yu-Jiao Z, Shu-Fang N, Jun C, Qian W et al (2015) Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals. Chin J Nat Med 13:641–652Google Scholar
- 18.Lee MS, Dees EC, Wang AZ (2017) Nanoparticle-delivered chemotherapy: old drugs in new packages. Oncology J 31:198–208Google Scholar
- 25.Saad EA, Habib SA, Refai WA, Elfayoumy AA (2017) Malondialdehyde, adiponectin, nitric oxide, C-reactive protein, tumor necrosis factor-alpha and insulin resistance relationships and inter-relationships in type 2 diabetes early stage. Is metformin alone adequate in this stage? Int J Pharm Pharm Sci 9(10):176–181. https://doi.org/10.22159/ijpps.2017v9i10.21149 CrossRefGoogle Scholar
- 26.Saad EA, Hassanien MM, El-Hagrasy MA, Radwan KH (2015) Antidiabetic, hypolipidemic and antioxidant activities and protective effects of Punica granatum peels powder against pancreatic and hepatic tissues injuries in streptozotocin induced IDDM in rats. Int J Pharm Pharm Sci 7(7):397–402. https://innovareacademics.in/journals/index.php/ijpps/article/view/6705/2649
- 27.Saad EA, Toson EA, Ahmed GM (2015) Clove or green tea administration antagonizes khat hepatotoxicity in rats. Int J Pharm Pharm Sci 7(6):72–76Google Scholar
- 28.Saad EA, Habib SA (2013) Effect of crude extracts of some medicinal plants on the osmotic stability of human erythrocytes in vitro. J Free Rad Antioxidants Photon 139:265–272. https://sites.google.com/site/photonfoundationorganization/home/the-journal-of-freeradicals-and-antioxidants
- 29.Toson EA, Habib SA, Saad EA, Harraz NH (2014) Toxic and anti-fertility effects of Alocasia macrorrhiza and Calotropis procera ethanolic extracts on male mice. Int J Biochem Photon 195:328–338. https://sites.google.com/site/photonfoundationorganization/home/internationaljournal
- 36.Vaja F, Guran C, Ficai D, Ficai A, Oprea O (2014) Cytotoxic effects of ZnO nanoparticles incorporated in mesoporous silica. UPB Sci Bull 76:55–66Google Scholar
- 37.Dickson MA, Schwartz GK (2009) Development of cell-cycle inhibitors for cancer therapy. Curr Oncol 16:36–43Google Scholar