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
DOI:
https://doi.org/10.56511/JIPBS.2015.v2.i04.pp506-521Abstract
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
References
WHO: The World Health Report 2008 – primary health care: Now more than ever. [http://www.who.int/whr/2008/ whr08_en.pdf]
Mondal J, Panigrahi AK, Khuda-Bukhsh AR: Conventional Chemotherapy: Problems and Scope for Combined Therapies with Certain Herbal Products and Dietary Supplements. Austin Journal of Molecular and Cellular Biology. 2014; 1:
Rabik CA, Dolan ME: Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 2007; 33: 9 – 23
Anderson ME, Naganuma A, Meister A: Protection against cisplatin toxicity by administration of glutathione ester. FASEB J. 1990; 4: 3251 – 3255.
Brady HR, Kone BC, Stromski ME, Zeidel ML, Giebisch G, Gullans SR: Mitochondrial injury: an early event in cisplatin toxicity to renal proximal tubules. Am J Physiol. 1990; 258:1181 – F1187.
O’Brien P, Carrasco -Pozo C, Speisky H: Boldine and its antioxidant or healthpromoting properties. Chemico-Biological Interactions. 2006; 159:1-17
Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S: Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int. J. Pharm. 1989; 55:1 – 4. doi:10.1016/0378-5173(89)90281-0
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X: Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997; 91:479 – 489.
Bhattacharyya SS, Paul S, De A, Das D, Samadder A, Boujedaini N, Khuda-Bukhsh AR: Poly (lactide-co-glycolide) acid nanoencapsulation of a synthetic coumarin: cytotoxicity and biodistribution in mice, in cancer cell line and interaction with calf thymus DNA as target. Toxicol Appl Pharmacol. 2011; 253:270-281. Doi: doi: 10.1016/j. taap.2011.04.010.
Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65:55 – 63.
Hissin PJ, Hilf R: A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 1976; 74: 214 – 226.
Battin EE, Brumaghim JL: Antioxidant activity of sulfur and selenium: a review of reactive oxygen species scavenging, glutathione peroxidase, and metal-binding antioxidant mechanisms. Cell Biochem Biophys. 2009; 55:1 – 23.
Sharma SS, Dietz KJ: The relationship between metal toxicity and cellular redox imbalance. Trends Plant Sci. 2009; 14:43 – 50.
Sheehan D, Meade G, Foley VM, Dowd CA: Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J. 2001; 360:1 – 16.
Snoke JE, Bloch K: Studies on the mechanism of action of glutathione synthetase. J Biol Chem. 1955; 213:825 – 835.
Haupt S, Berger M, Goldberg Z, Haupt Y: Apoptosis — the p53 network. J Cell Sci. 2003; 116: 4077 – 4085.
Zhang Z, Tsai PC, Ramezanli T, MichniakKohn BB: Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013; 5:205-218. Doi: doi: 10.1002/wnan. 1211.
Samadder A, Das J, Das S, De A, Saha SK, Bhattacharyya SS, Khuda-Bukhsh AR: Poly(lactic-co-glycolic) acid loaded nanoinsulin has greater potentials of combating arsenic induced hyperglycemia in mice: some novel findings. Toxicol. Appl. Pharmacol. 2013; 267:57 – 73.
Das S, Das J, Samadder A, Bhattacharyya SS, Das D, Khuda-Bukhsh AR: Biosynthesized silver nanoparticles by ethanolic extracts of Phytolacca decandra, Gelsemium sempervirens, Hydrastis canadensis and Thuja occidentalis induce differential cytotoxicity through G2/M arrest in A375 cells. Colloids Surf. B: Biointerfaces. 2013; 101:325 – 336.
Weissenbock A, Wirth M, Gabor F: WGAgrafted PLGA-nanospheres: preparation and association with Caco-2 single cells. J Control Release. 2004; 99:383-392.
Yallapu MM, Gupta BK, Jaggi M, Chauhan SC: Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. J Colloid Interface Sci. 2010; 351:19-
Doi: doi: 10.1016/j.jcis.2010.05.022.
Jain RA: The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials. 2000; 21:2475-2490.
Feng SS: Nanoparticles of biodegradable polymers for newconcept chemotherapy. Expert Review of Medical Devices. 2004; 1:115 – 125.
Suh H, Jeong B, Rathi R, Kim SW: Regulation of smooth muscle cell proliferation using paclitaxel-loaded poly(ethylene oxide)-poly(lactide/ glycolide) nanospheres. Journal of Biomedical Materials Research. 1998; 42:331 – 338.
Panyam J, Zhou WZ, Prabha S, Sahoo SK, Labhasetwar V: Rapid endolysosomal escape of poly(d,l-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB Journal. 2002; 16:1217 – 1226.
Gonzalez-Velasco JR, Lopez-Fonseca R, Aranzabal A, Gutierrez-Ortiz JI, Steltenpohl P, Mogi T, Ohtake N, Yoshida M, Chimura R, Kamaga Y, Ando S, Tsukamoto T, Nakajima T, Uenodan H, Otsuka M, Matsuda Y, Ohshima H, Makino K: Sustained release of 17b-estradiol from poly(lactidecoglycolide) microspheres in vitro and in vivo. Colloids and Surfaces B: Biointerfaces. 2000; 17:153 – 165.
Makino K, Mogi T, Ohtake N, Yoshida M, Ando S, Nakajima T, Ohshima H: Pulsatile drug release from poly(lactide-coglycolide) micro-spheres: how does composition of the polymer matrix affect the time interval between the initialburst and the pulsatile release of drugs? Colloids and Surfaces B: Biointerfaces. 2000; 19:173 – 179.
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