Loading of some quinoxaline derivatives in poly (l-lactic) acid/Pluronic® F-127 nanofibers enhances their anticancer efficiency and induces a p53 and p21 apoptotic-signaling pathway.

The objective of this study was to evaluate the anticancer activity on cancer cell models of a drug delivery system consisting of poly (l-lactic) acid/Pluronic® F-127 (PLLA/PF127) loaded with the new N-butylpyridoquinoxaline 1,4-dioxide (NBPQD) or 2-amino-3-cyano-6-methylquinoxaline 1,4-dioxide (ACMQD) that was synthesized using an electrospinning process compared to free NBPQD and ACMQD. PLLA/PF127-NBPQD and PLLA/PF127-ACMQD nanofibers were prepared, and their shape, size, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric (TGA) analysis, water contact angel (WCA), drug release, anticancer activity against five human cancer cell lines, and flowcytometeric analyses of cell cycle, p21 and p53 activities were investigated. PLLA/PF127 nanofibers with NBPQD or ACMQD were smooth, and no NBPQD or ACMQD clusters were found on nanofibers surface. FTIR analysis indicated that intermolecular hydrogen bonding between NBPQD or ACMQD and the polymer matrix is present. PLLA/PF127 nanofibers with NBPQD or ACMQD showed quite stable thermal stability with degradation at about 400 °C, and showed high WCA values of 68.72 ± 3.83° and 110.59 ± 0.21°, respectively. They showed higher in vitro anticancer activity towards all investigated cell lines compared to free NBPQD or free ACMQD. The lowest IC50 value for PLLA/PF127-NBPQD was 1.7 μg/ml with colorectal carcinoma (HCT-116) and was 4.5 μg/ml for PLLA/PF127-ACMQD with hepatocellular carcinoma (HepG2). PLLA/PF127 nanofibers with NBPQD or ACMQD increased anticancer efficiency via inducing cancer cell apoptosis through activation of a p53 and p21 apoptotic-signaling pathway.