Abstract
In the present study, magnetic nanoparticles (MNPs) were coated with chitosan (CS) polymer to form CS–MNP nanoparticles. The CS–MNP were loaded with an anticancer drug, betulinic acid (BA) to form a BA–CS–MNP nanocomposite. The prepared nanocomposite was characterized using XRD, FTIR, TGA, VSM, SEM, TEM, and zeta potential techniques. The release behavior of the BA from the nanocomposite was investigated at pH 7.4, and the study found that the release of BA followed a pseudo-second-order kinetic model. The potential cytotoxicity of free BA, MNPs, CS–MNP, and the BA–CS–MNP nanocomposite was evaluated using normal mouse fibroblast cells (3T3) and breast cancer cells (MCF-7). BA and the nanocomposite at concentrations in the range 0.781–50 μg mL−1 did not affect the viability of normal cells during 72 h of incubation. The BA and BA–CS–MNP nanocomposite exhibited cytotoxicity in MCF-7 cells in a dose-dependent manner with IC50 values of 2 and 3.6 μg mL−1, respectively.
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References
Pisha E et al (1995) Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med 1(10):1046–1051
Zuco V et al (2002) Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells. Cancer Lett 175(1):17–25
Wick W et al (1999) Betulinic acid-induced apoptosis in glioma cells: a sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. J Pharmacol Exp Ther 289(3):1306–1312
Ji Z-N et al (2002) 23-Hydroxybetulinic acid-mediated apoptosis is accompanied by decreases in bcl-2 expression and telomerase activity in HL-60 cells. Life Sci 72(1):1–9
Thurnher D et al (2003) Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells. Head Neck 25(9):732–740
Kim JY et al (2001) Development of C-20 modified betulinic acid derivatives as antitumor agents. Bioorg Med Chem Lett 11(17):2405–2408
Chatterjee P et al (2000) Biotransformation of the antimelanoma agent betulinic acid by Bacillus megaterium ATCC 13368. Appl Environ Microbiol 66(9):3850–3855
Hussein-Al-Ali SH et al (2014) Arginine–chitosan- and arginine–polyethylene glycol-conjugated superparamagnetic nanoparticles: preparation, cytotoxicity, and controlled-release. J Biomater Appl [Epub ahead of print]
Dilnawaz F et al (2010) Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 31(13):3694–3706
Qu J-B et al (2013) PEG-chitosan-coated iron oxide nanoparticles with high saturated magnetization as carriers of 10-hydroxycamptothecin: preparation, characterization and cytotoxicity studies. Colloid Surf B 102(1):37–44
Wang YX et al (2001) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11(11):2319–2331
Mahmoudi M et al (2009) Cell toxicity of superparamagnetic iron oxide nanoparticles. J Colloid Interface Sci 336(2):510–518
Xu ZP et al (2006) Inorganic nanoparticles as carriers for efficient cellular delivery. Chem Eng Sci 61(3):1027–1040
Chen Y-C et al (2012) In vitro evaluation of the L-peptide modified magnetic lipid nanoparticles as targeted magnetic resonance imaging contrast agent for the nasopharyngeal cancer. J Biomater Appl 28(4):580–594
Inbaraj BS et al (2011) The synthesis and characterization of poly (gamma-glutamic acid)-coated magnetite nanoparticles and their effects on antibacterial activity and cytotoxicity. Nanotechnology 22(7):075101
Li Z et al (2011) Preparation of magnetic iron oxide nanoparticles for hyperthermia of cancer in a FeCl2–NaNO3–NaOH aqueous system. J Biomater Appl 25(7):643–661
Zheng SW et al (2013) RGD-conjugated iron oxide magnetic nanoparticles for magnetic resonance imaging contrast enhancement and hyperthermia. J Biomater Appl 28(7):1051–1059
Panos I et al (2008) New drug delivery systems based on chitosan. Curr Drug Discov Technol 5(4):333–341
Unsoy G et al (2012) Synthesis optimization and characterization of chitosan-coated iron oxide nanoparticles produced for biomedical applications. J Nanopart Res 14(11):1–13
Predoi D (2007) A study on iron oxide nanoparticles coated with dextrin obtained by coprecipitation. Dig J Nanomater Biostruct 2:169–173
Inbaraj BS et al (2012) Synthesis, characterization and antibacterial activity of superparamagnetic nanoparticles modified with glycol chitosan. Sci Technol Adv Mater 13(1):37–44
Kumar SR et al (2014) Hydrophilic polymer coated monodispersed Fe3O4 nanostructures and their cytotoxicity. Mater Res Express 1(1):015015
Kayal S, Ramanujan RV (2010) Anti-cancer drug loaded iron–gold core-shell nanoparticles (FeAu) for magnetic drug targeting. J Nanosci Nanotechnol 10(9):5527–5539
Mandal M et al (2005) Magnetite nanoparticles with tunable gold or silver shell. J Colloid Interface Sci 286(1):187–194
Li P et al (2004) Synthesis and characterization of a high oil-absorbing magnetic composite material. J Appl Polym Sci 93(2):894–900
Sun J et al (2007) Synthesis and characterization of biocompatible Fe3O4 nanoparticles. J Biomed Mater Res A 80(2):333–341
Kumar R et al (2010) Surface modification of superparamagnetic iron nanoparticles with calcium salt of poly (gamma-glutamic acid) as coating material. Mater Res Bull 45(11):1603–1607
Marchessault RH et al (2006) Polysaccharides for drug delivery and pharmaceutical applications. American Chemical Society, Washington, DC
Soica CM et al (2012) Physico-chemical comparison of betulinic acid, betulin and birch bark extract and in vitro investigation of their cytotoxic effects towards skin epidermoid carcinoma (A431), breast carcinoma (MCF7) and cervix adenocarcinoma (HeLa) cell lines. Nat Prod Res 26(10):968–974
Shan Z et al (2007) Preparation and characterization of carboxyl-group functionalized superparamagnetic nanoparticles and the potential for bio-applications. J Braz Chem Soc 18(7):1329–1335
Gupta R, Bajpai AK (2012) Superparamagnetic nanocomposites of poly (vinyl alcohol-graft-acrylonitrile) as carrier for magnetically assisted release of ciprofloxacin. Macromol Symp 315(1):73–83
Hussein-Al-Ali SH et al (2014) Synthesis, characterization and antimicrobial activity of a novel ampicillin-conjugated magnetic nano-antibiotic. Int J Nanomed 9
Dong L et al (2010) Synthesis and release behavior of composites of camptothecin and layered double hydroxide. J Solid State Chem 183(8):1811–1816
Ho YS, Ofomaja AE (2006) Pseudo-second-order model for lead ion sorption from aqueous solutions onto palm kernel fiber. J Hazard Mater 129(1–3):137–142
Sakore S, Chakraborty B (2013) Formulation and evaluation of enalapril maleate sustained release matrix tablets. Int J Pharm 4(1):21–26
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The Ministry of Higher Education of Malaysia (MOHE) provided funding for this research under Grant No. 05-03-10-1035 RUGS (vote 9199644).
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Hussein-Al-Ali, S.H., Arulselvan, P., Fakurazi, S. et al. The in vitro therapeutic activity of betulinic acid nanocomposite on breast cancer cells (MCF-7) and normal fibroblast cell (3T3). J Mater Sci 49, 8171–8182 (2014). https://doi.org/10.1007/s10853-014-8526-3
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DOI: https://doi.org/10.1007/s10853-014-8526-3