Physico-chemical and ultra-structural characterizations of PLGA-loaded nanoparticles of Boldine and their efficacy in ameliorating cisplatin induced hepatotoxicity in normal liver cells in vitro
Abstract
Production of unwanted hepatotoxicity and side-effects often restrict use of cisplatin as a chemotherapeutic agent in oncology. Therefore, this study was conducted for testing if co-administration of poly (lactic-co-glycolide) (PLGA)-loaded Boldine (NBol), an active alkaloid ingredient of Boldo (Peumus boldus) plant reported to have cytoprotective property could alleviate cisplatin-induced toxicity better than Boldine (Bol) in normal liver cells (WRL-68) but not protecting liver cancer cells (HepG2). NBol were prepared by adopting the standard solvent displacement method and characterized for their size, morphology and zeta potential by using dynamic light scattering, atomic force-, scanning- and transmission-electron microscopies, and fourier transform infra-red spectroscopy. Cellular entry was also demonstrated with the aid of fluorescence microscopy. The entrapment efficiency, percent yield, in vitro release kinetics and protective effects of NBol were analyzed by studying cellular morphology of liver cells, MTT assay, and cytotoxicity assay. Expression of different proteins related to cytotoxicity and cell survival were critically studied by western blotting and confocal microscopy. Boldine loaded PLGA nanoparticles were successfully prepared with 84.19 ± 1.72% yield in the nanometer range and had 81.93 ± 0.915% encapsulation efficiency. Co-administration of NBol and cisplatin produced better and faster site-specific action than that of Bol due to former’s smaller size (115.5±0.469nm) and negative zeta potential (-17.4±2.38 mV). Co-administration of NBol protected normal cells from cisplatin-induced hepatotoxicity, but had no or negligible protective effects in cancer cells. Thus, NBol had greater potential of being used as a supportive therapy along with cisplatin in the treatment of cancer
Keywords:
PLGA- Nano-encapsulation, Boldine, Cisplatin, Hepatotoxicity, DNA-targeting, CytoprotectionDownloads
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Copyright (c) 2015 Jesmin Mondal, Ashis Kumar Panigrahi, Anisur Rahman Khuda-Bukhsh
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