Evaluation of the cytotoxic and genotoxic potential of lecithin/chitosan nanoparticles
Source abstract
Abstract
Nanoparticles-based drug targeting deliv- ery systems have been introduced in the treatment for various diseases because of their effective properties, although there have been conflicting results on the toxicity of nanoparticles. In the present study, the aim was to evaluate the cytotoxicity and the genotoxicity of different concentrations of lecithin/chitosan nano- particles with and without clobetasol-17-propionate (CP) by neutral red uptake (NRU) cytotoxicity assay and single cell gel electrophoresis (Comet) and cytokinesis-blocked micronucleus assays. The IC50 values of lecithin/chitosan nanoparticles with/without CP were found as 1.9 and 1.8 %, respectively, in the NRU cytotoxicity test. High concentrations of leci- thin/chitosan nanoparticles induced DNA damage in human lymphocytes as evaluated by comet assay. The micronucleus frequency was increased by the lecithin/ chitosan treatment in a dose-dependent manner. Also at the two highest concentrations, a significant increase in micronucleus formation was observed. Lecithin/chitosan nanoparticles with CP did not increase the frequency of micronucleus and also did not induce additional DNA damage when compared with lecithin/chitosan nanoparticles without CP; therefore, CP itself has not found to be genotoxic at the studied concentration.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: RNA Interference and Gene Delivery · Advanced Drug Delivery Systems · Advanced biosensing and bioanalysis techniques
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (38)
Show source-provided references
1. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM (2004) Recent advances on chitosan based micro- and nanoparticles in drug delivery. J Control Release 100:5–2810.1016/j.jconrel.2004.08.010 ↗
2. Anderson D, Yu TW, Phillips BJ, Schmezer P (1994) The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay. Mutat Res 307:261–27110.1016/0027-5107(94)90300-X ↗
3. Banasik A, Lankoff A, Piskulak A, Adamowska K, Lisowska H, Wojcik A (2005) Aluminum-induced micronuclei and apoptosis in human peripheral-blood lymphocytes treated during different phases of the cell cycle. Environ Toxicol 20(4):402–40610.1002/tox.20125 ↗
4. Batzri S, Korn E (1973) Single bilayer liposomes prepared without sonication. Biochim Biophys Acta 298:1015–101910.1016/0005-2736(73)90408-2 ↗
5. Boyum A (1976) Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol 5:9–1510.1111/j.1365-3083.1976.tb03851.x ↗
6. Collins AR, Dobson VL, Dusinska M, Kennedy G, Stetina R (1997) The comet assay: what can it really tell us? Mutat Res 375(2):183–19310.1016/S0027-5107(97)00013-4 ↗
7. De Lima R, Feitosa L, A Do Espírito Santo Pereira, De Moura MR, Ahmad Aouada F, Henrique Capparelli Mattoso L, Fernandes Fraceto L (2010) Evaluation of the genotoxicity of chitosan nanoparticles for use in food packaging films. J Food Sci 75(6):89–9610.1111/j.1750-3841.2010.01682.x ↗
8. Dodane V, Amin Khan M, Merwin JR (1999) Effect of chitosan on epithelial permeability and structure. Int J Pharm 182(1):21–3210.1016/S0378-5173(99)00030-7 ↗
9. El-Zein RA, Schabath MB, Etzel CJ, Lopez MS, Franklin JD, Spitz MR (2006) Cytokinesis-blocked micronucleus assay as a novel biomarker for lung cancer risk. Cancer Res 66:6449–645610.1158/0008-5472.CAN-06-0326 ↗
10. Felt O, Buri P, Gurny R (1998) Chitosan: a unique polysaccharide for drug delivery. Drug Dev Ind Pharm 24:979–99310.3109/03639049809089942 ↗
11. Fenech M (2000) The micronucleus technique. Mutat Res 455:81–9510.1016/S0027-5107(00)00065-8 ↗
12. Fernandes JC, Borges M, Nascimento H, Bronze-da-Rocha E, Ramos OS, Pintado ME, Malcata FX, Santos-Silva A (2011) Cytotoxicity and genotoxicity of chitooligosaccharides upon lymphocytes. Int J Biol Macromol 49(3):433–43810.1016/j.ijbiomac.2011.05.032 ↗
13. Franz TJ, Lehman PA, Feldman SR, Spellman MN (2003) Bioavailability of clobetasol propionate in different vehicles, skin pharmacol. Appl Skin Physiol 16:212–21610.1159/000070843 ↗
14. Gonzalez L, Dominique Lison D, Kirsch-Volders M (2008) Genotoxicity of engineered nanomaterials: a critical review. Nanotoxicology 2(4):252–27310.1080/17435390802464986 ↗
15. Haas J, Kumar MNVR, Borchard G, Bakowsky U, Lehr CM (2005) Preparation and characterization of chitosan and trimethyl-chitosan modified poly-(e-caprolactone) nanoparticles as DNA Carriers. AAPS PharmSciTech, E22-E3010.1208/pt060106 ↗
16. Hu YL, Qi W, Han F, Shao JZ, Gao JQ (2011) Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. Int J Nanomed 6:3351–3359
17. Illum L (1998) Chitosan and its use as a pharmaceutical excipient. Pharm Res 15:1326–133110.1023/A:1011929016601 ↗
18. Karlsson HL (2010) The comet assay in nanotoxicology research. Anal Bioanal Chem 398(2):651–65610.1007/s00216-010-3977-0 ↗
19. Kompella UB, Bandi N, Ayalasomayajula SP (2003) Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting vegf expression. Investig Ophthalmol Vis Sci 44:1192–120110.1167/iovs.02-0791 ↗
20. Krishna G, Kropko ML, Theiss JC (1989) Use of the cytokinesis-block method for the analysis of micronuclei in V79 Chinese hamster lung cells: results with mytomycin C and cyclophosphamide. Mutat Res Genet Toxicol 222:63–6910.1016/0165-1218(89)90036-0 ↗
21. Limbach LK, Li Y, Grass RN, Brunner TJ, Hintermann MA, Muller M, Gunther D, Stark WJ (2005) Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration and diffusion at low concentrations. Environ Sci Technol 39:9370–937610.1021/es051043o ↗
22. Loh JW, Yeoh G, Saunders M, Lim LY (2010) Uptake and cytotoxicity of chitosan nanoparticles in human liver cells. Toxicol Appl Pharmacol 249(2):148–15710.1016/j.taap.2010.08.029 ↗
23. Mu X, Li Z, Li X, Mishra SR, Zhang B, Si Z, Yang L, Jiang W, Yan B (2009) Characterization of protein clusters of diverse magnetic nanoparticles and their dynamic interactions with human cells. J Phys Chem 113:5390–5395
24. Nagpal K, Singh SK, Mishra DN (2010) Chitosan nanoparticles: a promising system in novel drug delivery. Chem Pharm Bull 58(11):1423–143010.1248/cpb.58.1423 ↗
25. Nel A, Xia T, Mädler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311(5761):622–62710.1126/science.1114397 ↗
26. Qi L, Xu Z, Chen M (2007) In vitro and in vivo suppression of hepatocellular carcinoma growth by chitosan nanoparticles. Eur J Cancer 43:184–19310.1016/j.ejca.2006.08.029 ↗
27. Saquib Q, Al-Khedhairy AA, Siddiqui MA, Abou-Tarboush FM, Azam A, Musarrat J (2012) Titanium dioxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in human amnion epithelial (WISH) cells. Toxicol In Vitro 26:351–36110.1016/j.tiv.2011.12.011 ↗
28. Şenyiğit T, Sonvico F, Barbieri S, Ozer O, Santi P, Colombo P (2010) Lecithin/chitosan nanoparticles of clobetasol-17-propionate capable of accumulation in pig skin. J Control Release 142(3):368–37310.1016/j.jconrel.2009.11.013 ↗
29. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–19110.1016/0014-4827(88)90265-0 ↗
30. Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG, Wright CJ, Doak SH (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30(23–24):3891–391410.1016/j.biomaterials.2009.04.009 ↗
31. Singla AK, Chawla M (2001) Chitosan: some pharmaceutical and biological aspects an update. J Pharm Pharmacol 53:1047–106710.1211/0022357011776441 ↗
32. Sonvico F, Cagnani A, Rossi A, Motta S, Di Bari MT, Cavatorta F, Alonso MJ, Deriu A, Colombo P (2006) Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction. Int J Pharm 324:67–7310.1016/j.ijpharm.2006.06.036 ↗
33. Surrales J, Xamena N, Creus A, Catalan J, Norppa H, Marcos R (1995) Induction of micronuclei by five pyrethroid insecticides in whole blood and isolated human lymphocytes cultures. Mutat Res 341:169–18410.1016/0165-1218(95)90007-1 ↗
34. Thevenot P, Hu W, Tang L (2008) Surface chemistry influences implant biocompatibility. Curr Top Med Chem 8:270–28010.2174/156802608783790901 ↗
35. Vandghanooni S, Eskandani M (2011) Comet assay: a method to evaluate genotoxicity of nano-drug delivery system. BioImpacts 1(2):87–97
36. Virgilio ALD, Iwami K, Wätjen W, Kahl R, Degen GH (2004) Genotoxicity of the isoflavones genistein, daidzein and equol in V79 cells. Toxicol Lett 151:151–16210.1016/j.toxlet.2004.04.005 ↗
37. Xia T, Kovochich M, Liong M, Zink JI, Nel AE (2008) Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano 2:85–9610.1021/nn700256c ↗
38. Zeng R, Tu M, Liu H, Zhao J, Zha Z, Zhou C (2009) Preparation, structure, drug release and bioinspired mineralization of chitosan-based nanocomplexes for bone tissue engineering. Carbohydr Polym 78:107–11110.1016/j.carbpol.2009.04.035 ↗