الفهرس 
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Abstract
This study was proposed to design and characterize biodegradable (1) poly (lactic-co-glycolic acid) (PLGA) nanospheres loaded with the new N-butylpyridoquinoxaline 1,4-dioxide (NBPQD) and (2) poly (L-lactic)-acid/Pluronic® F-127 (PLLA/PF127) nanofibers loaded with NBPQD or with 2-amino-3-cyano-6-methyl quinoxaline1,4- dioxide (ACMQD) in addition to (3) PLLA/PF127 nanospheres loaded with ACMQD to investigate the potential anticancer activities of these newly designed nanoforms against their free (non-nano) forms.
In vitro studies
PLGA nanospheres loaded with NBPQD
TEM images showed that the prepared nanoparticles are spherical in shape with diameter of 54 nm. Zeta potential equals − 20.4 ± 7.04 mV.Encapsulation efficiency and actual drug loading were 88% and 21.8 ± 0.25%, respectively.Drug release from PLGA nanospheres was an initial burst phase corresponding to about 30–35% within 1 h then a sustained NBPQD release to a total of about 65–70% .PLGA-NBPQD showed more pronounced cytotoxicities against the studied human cancer cells (MCF-7, Hep2, HCT-116, PC3, HepG2, and Hela) than free NBPQD.
PLLA/PF127 nanofibers loaded with NBPQD or with ACMQD
SEM images emphasize that drugs were uniformly distributed in nanofibers, and their average diameter was increased. Thermal degradation actions were significantly higher than thermal decomposition of pure Nano fibers. An initial burst phase equivalent to 35-37% of loaded drugs was detected within the first several hours of the first day with a sustained release to a maximum of nearly 70% by the end. incorporation of drugs in nanofibers resulted in pronounced significant improves in drug cytotoxicity. The levels of p53 and p21 are significantly elevated in cells treated with drugs nanofibers and free drugs compared with negative control cell line.
PLLA/ PF127 nanospheres loaded with ACMQD TEM images showed that the prepared nanoparticles are spherical in shape with a mean diameter of 100 nm. Zeta potential equals - 7.8 ± 5.0 mV. Encapsulation efficiency were 92.3±1.95% and 22.8 ± 0.3%, it showed more pronounced cytotoxicity against HepG2 cells than free ACMQD. In vivo study Untreated DEN rats showed significant reductions in body weight gain, Hb, RBCs count, albumin, total protein, GSH, GPx, catalase and SOD activities along with significant elevations in WBCs, platelets count, liver enzymes activities, AFP, MDA, cholesterol, trigacylglycerols, creatinine and urea concentration compared with our drugs. Finally, loading of NBPQD or ACMQD into a polymeric nanocarrier could be an ideal technique for improving its pharmacological effects and maintaining its long-term antitumor efficacy, which might be, after more validation, used for future cancer treatment.