Poly(butyl cyanoacrylate) nanoparticles stabilised with poloxamer 188: particle size control and cytotoxic effects in cervical carcinoma (HeLa) cells
Abstract
In this study, the preparation of poloxamer 188-coated poly(butyl cyanoacrylate) colloidal nanospheres of controlled size distribution and their physicochemical characterisation were investigated and their cytotoxic effects in cervical carcinoma (HeLa) cells evaluated. The nanoparticles were prepared by controlled emulsion polymerisation of butyl cyanoacrylate in an aqueous medium containing poloxamer 188 as an amphiphilic non-ionic colloidal stabiliser. The colloids thus obtained were characterised by scanning electron microscopy, dynamic and electrophoretic light-scattering, Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The average size of the particles could be finely controlled within an interval between 220 nm and 290 nm by varying the concentration of the precursor and citric acid in the polymerisation medium. The particle zeta-potentials in phosphate-buffered saline were approximately -4.5 mV. FTIR and NMR data confirmed the expected composition of nanoparticles and the complete precursor polymerisation. In-vitro studies with cervical carcinoma (HeLa) cells demonstrated the dose-dependent cytotoxicity of nanoparticles (IC50 ≈ 30 μg mL-1). Observations by phase contrast and fluorescence microscopy revealed that at cytotoxic concentrations (40 μg mL-1) nanoparticles induced changes in cell morphology and chromatin fragmentation. The colloidal stabiliser (poloxamer 188) alone was not cytotoxic at the applied concentrations.
References
Aggarwal, P., Hall, J. B., McLeland, C. B., Dobrovolskaia, M. A., & McNeil, S. E. (2009). Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Advanced Drug Delivery Reviews, 61, 428-437. DOI: 10.1016/j.addr.2009.03.009.10.1016/j.addr.2009.03.009Suche in Google Scholar
Alonso, M. J., Sanchez, A., Torres, D., Seijo, B., & Vila-Jato, J. L. (1990). Joint effects of monomer and stabilizer concentrations on physico-chemical characteristics of poly(butyl 2-cyanoacrylate) nanoparticles. Journal of Microencapsulation, 7, 517-526. DOI: 10.3109/02652049009040475.10.3109/02652049009040475Suche in Google Scholar
Ambruosi, A., Khalansky, A. S., Yamamoto, H., Gelperina, S. E., Begley, D. J., & Kreuter, J. (2006). Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats. Journal of Drug Targeting, 14, 97-105. DOI: 10.1080/10611860600636135.10.1080/10611860600636135Suche in Google Scholar
Arias, J. L., Gallardo, V., Ruiz, M. A., & Delgado, A. V. (2008). Magnetite/poly(alkylcyanoacrylate) (core/shell) nanoparticles as 5-fluorouracil delivery systems for active targeting. European Journal of Pharmaceutics and Biopharmaceutics, 69, 54-63. DOI: 10.1016/j.ejpb.2007.11.002.10.1016/j.ejpb.2007.11.002Suche in Google Scholar
Behan, N., Birkinshaw, C., & Clarke, N. (2001). Poly n-butyl cyanoacrylate nanoparticles: a mechanistic study of polymerisation and particle formation. Biomaterials, 22, 1335-1344. DOI: 10.1016/s0142-9612(00)00286-6.10.1016/S0142-9612(00)00286-6Suche in Google Scholar
Cruz, T., Gaspar, R., Donato, A., & Lopes, C. (1997). Interaction between polyalkylcyanoacrylate nanoparticles and peritoneal macrophages: MTT metabolism, NBT reduction, and NO production. Pharmaceutical Research, 14, 73-79.10.1023/A:1012059501947Suche in Google Scholar
Douglas, S. J., Illum, L., Davis, S. S., & Krueter, J. (1984). Particle size and size distribution of poly(butyl-2-cyanoacrylate) nanoparticles: I. Influence of physicochemical factors. Journal of Colloid and Interface Science, 101, 149-158. DOI: 10.1016/0021-9797(84)90015-8.10.1016/0021-9797(84)90015-8Suche in Google Scholar
Douglas, S. J., Davis, S. S., & Holding, S. R. (1985). Molecular weights of poly(butyl 2-cyanoacrylate) produced during nanoparticle formation. British Polymer Journal, 17, 339-342. DOI: 10.1002/pi.4980170404.10.1002/pi.4980170404Suche in Google Scholar
Douglas, S. J., Illum, L., & Daviss, S. S. (1986). Poly(butyl 2- cyanoacrylate) nanoparticles with differing surface charges. Journal of Controlled Release, 3, 15-23. DOI: 10.1016/0168-3659(86)90060-x.10.1016/0168-3659(86)90060-XSuche in Google Scholar
Evangelatov, A., Skrobanska, R., Mladenov, N., Petkova, M., Yordanov, G., & Pankov, R. (2014). Epirubicin loading in poly(butyl cyanoacrylate) nanoparticles manifests via altered intracellular localization and cellular response in cervical carcinoma (HeLa) cells. Drug Delivery. DOI: 10.3109/10717544.2014.962117. (in press) 10.3109/10717544.2014.962117Suche in Google Scholar PubMed
Gulyaev, A. E., Gelperina, S. E., Skidan, I. N., Antropov, A. S., Kivman, G. Y., & Kreuter, J. (1999). Significant transport of doxorubicin into the brain with Polysorbate 80- coated nanoparticles. Pharmaceutical Research, 16, 1564-1569. DOI: 10.1023/a:1018983904537.10.1023/A:1018983904537Suche in Google Scholar
Hashizume, H., Baluk, P., Morikawa, S., McLean, J. W., Thurston, G., Roberge, S., Jain, R. K., & McDonald, D. M. (2000). Openings between defective endothelial cells explain tumor vessel leakiness. The American Journal of Pathology, 156, 1363-1380. DOI: 10.1016/s0002-9440(10)65006-7 10.1016/S0002-9440(10)65006-7Suche in Google Scholar
Kagan, V. E., Bayir, H., & Shvedova, A. A. (2005). Nanomedicine and nanotoxicology: two sides of the same coin. Nanomedicine: Nanotechnology, Biology, and Medicine, 1, 313-316. DOI: 10.1016/j.nano.2005.10.003.10.1016/j.nano.2005.10.003Suche in Google Scholar
Kante, B., Couvreur, P., Dubois-Krack, G., de Meester, C., Guiot, P., Roland, M.,Mercier,M., & Speiser, P. (1982). Toxicity of polyalkylcyanoacrylate nanoparticles I: Free nanoparticles. Journal of Pharmaceutical Science, 71, 786-790. DOI: 10.1002/jps.2600710716.10.1002/jps.2600710716Suche in Google Scholar
Kreuter, J., Wilson, C. G., Fry, J. R., Paterson, P., & Ratcliffe, J. H. (1984). Toxicity and association of polycyanoacrylate nanoparticles with hepatocytes. Journal of Microencapsulation, 1, 253-257. DOI: 10.3109/02652048409049364.10.3109/02652048409049364Suche in Google Scholar
Lherm, C., M¨uller, R. H., Puisieux, F., & Couvreur, P. (1992). Alkylcyanoacrylate drug carriers: II. Cytotoxicity of cyanoacrylate nanoparticles with different alkyl chain length. International Journal of Pharmaceutics, 84, 13-22. DOI: 10.1016/0378-5173(92)90210-s.10.1016/0378-5173(92)90210-SSuche in Google Scholar
Linkov, I., Satterstrom, F. K., & Corey, L. M. (2008). Nanotoxicology and nanomedicine: making hard decisions. Nanomedicine: Nanotechnology, Biology, and Medicine, 4, 167-171. DOI: 10.1016/j.nano.2008.01.001.10.1016/j.nano.2008.01.001Suche in Google Scholar
Maeda, H. (2012). Macromolecular therapeutics in cancer treatment: The EPR effect and beyond. Journal of Controlled Release, 164, 138-144. DOI: 10.1016/j.jconrel.2012.04.038.10.1016/j.jconrel.2012.04.038Suche in Google Scholar
Matsumura, Y., & Maeda, H. (1986). A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Research, 46, 6387-6392.Suche in Google Scholar
Müller, R. H., Lherm, C., Herbert, J., & Couvreur, P. (1990). In vitro model for the degradation of alkylcyanoacrylate nanoparticles. Biomaterials, 11, 590-595. DOI: 10.1016/0142-9612(90)90084-4.10.1016/0142-9612(90)90084-4Suche in Google Scholar
Murthy, R., & Reddy, L. (2006). Poly(alkyl cyanoacrylate) nanoparticles for delivery of anti-cancer drugs. In M. M. Amiji (Ed.). Nanotechnology for cancer therapy (pp. 251-288). Boca Raton, FL, USA: CRC Press.Suche in Google Scholar
Nicolas, J., & Couvreur, P. (2009). Synthesis of poly(alkyl cyanoacrylate)-based colloidal nanomedicines. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 1, 111-127. DOI: 10.1002/wnan.15.10.1002/wnan.15Suche in Google Scholar PubMed
Pereverzeva, E., Treschalin, I., Bodyagin, D., Maksimenko, O., Kreuter, J., & Gelperina, S. (2008). Intravenous tolerance of a nanoparticle-based formulation of doxorubicin in healthy rats. Toxicology Letters, 178, 9-19. DOI: 10.1016/j.toxlet. 2008.01.020.Suche in Google Scholar
Ren, H., & Huan, X. (2010). Polyacrylate nanoparticles: toxicity or new nanomedicine? European Respiratory Journal, 36, 218-221. DOI: 10.1183/09031936.00022410.10.1183/09031936.00022410Suche in Google Scholar
Sahay, G., Alakhova, D. Y., & Kabanov, A. V. (2010). Endocytosis of nanomedicines. Journal of Controlled Release, 145, 182-195. DOI: 10.1016/j.jconrel.2010.01.036.10.1016/j.jconrel.2010.01.036Suche in Google Scholar
Torchilin, V. (2011). Tumor delivery of macromolecular drugs based on the EPR effect. Advanced Drug Delivery Reviews, 63, 131-135. DOI: 10.1016/j.addr.2010.03.011.10.1016/j.addr.2010.03.011Suche in Google Scholar
Vansnick, L., Couvreur, P., Christiaens-Leyh, D., & Roland, M. (1985). Molecular weights of free and drug-loaded nanoparticles. Pharmaceutical Research, 2, 36-41. DOI: 10.1023/a:1016366022712.10.1023/A:1016366022712Suche in Google Scholar
Vauthier, C., Dubernet, C., Fattal, E., Pinto-Alphandary, H., & Couvreur, P. (2003). Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications. Advanced Drug Delivery Reviews, 55, 519-548. DOI: 10.1016/s0169-409x(03) 00041-3.Suche in Google Scholar
Yordanov, G., Abrashev, N., & Dushkin, C. (2010). Poly(nbutyl cyanoacrylate) submicron particles loaded with ciprofloxacin for potential treatment of bacterial infections. Progress in Colloid and Polymer Science, 137, 53-59. DOI: 10.1007/978-3-642-13461-6 11.10.1007/978-3-642-13461-6Suche in Google Scholar
Yordanov, G. (2012). Poly(alkyl cyanoacrylate) nanoparticles as drug carriers 33 years later. Bulgarian Journal of Chemistry, 1, 61-73.Suche in Google Scholar
Zhang, Z. R., Liao, G. T., Nagai, T., & Hou, S. X. (1996). Mitoxantrone polybutyl cyanoacrylate nanoparticles as an anti-neoplastic targeting drug delivery system. International Journal of Pharmaceutics, 139, 1-8. DOI: 10.1016/0378-5173(96)04550-4.10.1016/0378-5173(96)04550-4Suche in Google Scholar
Zhou, Q. H., Sun, X., Zeng, L. G., Liu, J., & Zhang, Z. R. (2009). A randomized multicenter phase II clinical trial of mitoxantrone-loaded nanoparticles in the treatment of 108 patients with unresected hepatocellular carcinoma. Nanomedicine: Nanotechnology, Biology and Medicine, 5, 419-423. DOI: 10.1016/j.nano.2009.01.009 10.1016/j.nano.2009.01.009Suche in Google Scholar PubMed
Institute of Chemistry, Slovak Academy of Sciences
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Artikel in diesem Heft
- Synthesis and properties of new N,N′-phenyltetrazole podand
- Molecular diagnosis of Pompe disease using MALDI TOF/TOF and 1H NMR
- Erythritol biosynthesis from glycerol by Yarrowia lipolytica yeast: effect of osmotic pressure
- Cloning and expression of two genes coding endo-β-1,4-glucanases from Trichoderma asperellum PQ34 in Pichia pastoris
- Adsorption desulphurisation of dimethyl sulphide using nickel-based Y zeolites pretreated by hydrogen reduction
- Equilibrium and kinetics of wetting hydrophobic microporous membrane in sodium dodecyl benzene sulphonate and diethanolamine aqueous solutions
- Separation of urea adducts in the analysis of complex mineral fertilisers
- Cheese whey tangential filtration using tubular mineral membranes
- Characterization of the quality of novel rye-buckwheat ginger cakes by chemical markers and antioxidant capacity
- A new high-temperature inorganic–organic proton conductor: lanthanum sulfophenyl phosphate
- Membranes with a plasma deposited titanium isopropoxide layer
- Effect of fuel content on formation of zinc aluminate nano and micro-particles synthesised by high rate sol–gel autoignition of glycine-nitrates
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