Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

Abstract

Purpose The normal metabolite methylglyoxal (MG) specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon normal cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest in developing a nanoparticulate drug delivery system to protect it and also to enhance its efficacy. Materials and methods MG-conjugated chitosan nanoparticles (Nano-MG) were prepared by conjugating the carbonyl group of MG with the amino group of chitosan polymer (Schiff’s base formation). Nano-MG were characterized in detail using the dynamic light scattering method, zeta potential measurement, Fourier transform infrared spectroscopy, and transmission electron microscopic analysis. Amount of MG anchored to Nano-MG, stability of Nano-MG, and in vitro release of MG from Nano-MG were estimated spectrophotometrically. Ehrlich ascites carcinoma (EAC) cells, human breast cancer cell line HBL-100, and lung epithelial adenocarcinoma cell line A549 were used as test systems to compare Nano-MG with bare MG in vitro. Cytotoxicity to EAC cells was evaluated by the trypan blue dye exclusion test, and cell viability of HBL-100 and A549 cells were studied using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of HBL-100 cells was assessed by flow cytometry and confocal microscopy. In vivo studies were performed on both EAC cells inoculated and also in sarcoma-180-induced solid tumor-bearing Swiss albino mice to assess the anticancer activity of Nano-MG in comparison to bare MG with varying doses, times, and administrative routes. Results Fourier transform infrared spectroscopy revealed the presence of imine groups in Nano-MG due to conjugation of the amino group of chitosan and carbonyl group of MG with diameters of nanoparticles ranging from 50–100 nm. The zeta potential of Nano-MG was +21 mV and they contained approximately 100 μg of MG in 1 mL of solution. In vitro studies with Nano-MG showed higher cytotoxicity and enhanced rate of apoptosis in the HBL-100 cell line in comparison with bare MG, but no detrimental effect on normal mouse myoblast cell line C2C12 at the concerned doses. Studies with EAC cells also showed increased cell death of nearly 1.5 times. Nano-MG had similar cytotoxic effects on A549 cells. In vivo studies further demonstrated the efficacy of Nano-MG over bare MG and found them to be about 400 times more potent in EAC-bearing mice and nearly 80 times more effective in sarcoma-180-bearing mice. Administration of ascorbic acid and creatine during in vivo treatments augmented the anticancer effect of Nano-MG. Conclusion The results clearly indicate that Nano-MG may constitute a promising tool in anticancer therapeutics in the near future.

<p>Potential of Methylglyoxal-Conjugated Chitosan Nanoparticles in Treatment of Fluconazole-Resistant <em>Candida albicans</em> Infection in a Murine Model</p>

“…In the present study, we determined the activity of MG and MGCN against C. albicans infection. Conjugation of MG to chitosan nanoparticles resulted in the increased activity of MG. 29,30 Candida albicans shows an ability to grow as unicellular budding yeast cell and filamentous hyphae form. The hyphae form is considered a virulent factor as compared to the yeast form of C. albicans.…”

“…The quantity of MG associated with nanoparticles was calculated by plotting the standard curve and then determining the amount of MG in an unknown sample using the standard plot. 29,30 Since MG does not have any aromatic ring for absorbance, we can use substrate for MG and subsequently plot standard curve for their product. About 200 µL of nanoparticle formulation was taken and treated with 0.5 M perchloric acid to release the entrapped MG.…”

Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

“…One of the major obstacles with using methylglyoxal as an anticancer agent is that methylglyoxal, being a normal metabolite, is rapidly degraded by various enzymes present in the body ( Pal et al, 2015 ; Ray & Ray, 1998 ). Naturally, there are several pathways to degrade methylglyoxal including methylglyoxal degradation I to VIII pathways.…”

“…In fact, a group of researchers has developed a nanofabrication of methylglyoxal with chitosan biopolymer, a nanoparticulate drug delivery system to protect it from degradation. This protection enhanced the efficacy of methylglyoxal as an anticancer drug in the tested Ehrlich ascites carcinoma, human breast cancer and lung epithelial adenocarcinoma cell lines that is augmented by creatine and ascorbic acid ( Pal et al, 2015 ).…”