Preparation and Evaluation of pH Sensitive Novel Anticancer Drug Carrier Based on Magnetic Chitosan Quartets

Abstract

Chitosan-coated magnetic nanoparticles are an appropriate drug delivery method which can improve the therapeutic properties of chemotherapy agents and also can be useful as MRI contrast agent for early cancer diagnosis. This research discovers the optimization of the possible therapeutic effects of Chitosan- citric acid- Fe₃O₄- CUR quartets. Chitosan as a natural polymer can use to encapsulate citric acid modified Fe₃O₄ nanoparticles. The successful preparation of CUR-loaded nano-carriers was confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) techniques. Moreover, the hemolysis test was used for the study of hemobiocompatibility. The loading capacity and encapsulation efficiency of CUR molecules were 11±0.09% and 49.5±0.41%, respectively. The anticancer effect of the void of CUR and CUR-loaded nano-carriers were compared by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the treated MCF-7 cell lines. It can be concluded that the use of these nanoparticles are a better and more efficient approach for the controlled and slow release of CUR in the cancer treatment.

Keywords

chitosan - citric acid - drug delivery - curcumin - magnetic nanoparticles

• References

• 1 Kumari P, Swami MO, Nadipalli SK. et al. Curcumin delivery by poly (Lactide)-based co-polymeric micelles: An in vitro anticancer study. Pharmaceutical research 2016; 33: 826-841
• 2 Caka M, Türkcan C, Aktaş Uygun D. et al. Controlled release of curcumin from poly (HEMA-MAPA) membrane, artificial cells. nanomedicine, and biotechnology 2017; 45: 426-431
• 3 Almeida EA, Bellettini IC, Garcia FP. et al. Curcumin-loaded dual pH-and thermo-responsive magnetic microcarriers based on pectin maleate for drug delivery. Carbohydrate Polymers 2017; 171: 259-266
• 4 Dorai T, Cao YC, Dorai B. et al. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. The prostate 2001; 47: 293-303
• 5 Liang H, Friedman JM, Nacharaju P. Fabrication of biodegradable PEG–PLA nanospheres for solubility, stabilization, and delivery of curcumin, artificial cells. nanomedicine, and biotechnology 2017; 45: 297-304
• 6 Bisht S, Feldmann G, Soni S. et al. Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): A novel strategy for human cancer therapy. Journal of nanobiotechnology 2007; 5: 3
• 7 Lao CD, Ruffin MT, Normolle D. et al. Dose escalation of a curcuminoid formulation. BMC complementary and alternative medicine 2006; 6: 10
• 8 Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer research 1986; 46 12 Part 1 6387-6392
• 9 Novelli F, De Santis S, Diociaiuti M. et al. Curcumin loaded nanocarriers obtained by self-assembly of a linear d, l-octapeptide-poly (ethylene glycol) conjugate. European Polymer Journal 2018; 98: 28-38
• 10 Chen Y, Peng F, Song X. et al. Conjugation of paclitaxel to C-6 hexanediamine-modified hyaluronic acid for targeted drug delivery to enhance antitumor efficacy. Carbohydrate polymers 2018; 181: 150-158
• 11 Agüero L, Zaldivar-Silva D, Peña L et al. Alginate microparticles as oral colon drug delivery device: A review. Carbohydrate Polymers 2017
• 12 Herrero MH, Gómez-Tejedor J, Vallés-Lluch A. PLA/PCL electrospun membranes of tailored fibres diameter as drug delivery systems. European Polymer Journal 2018
• 13 Wang L, Li B, Xu F. et al. UV-crosslinkable and thermo-responsive chitosan hybrid hydrogel for NIR-triggered localized on-demand drug delivery. Carbohydrate Polymers 2017; 174: 904-914
• 14 Soares PI, Sousa AI, Silva JC. et al. Chitosan-based nanoparticles as drug delivery systems for doxorubicin: Optimization and modelling. Carbohydrate polymers 2016; 147: 304-312
• 15 Zhao A, Yao P, Kang C. et al. Synthesis and characterization of tat-mediated O-CMC magnetic nanoparticles having anticancer function. Journal of magnetism and magnetic materials 2005; 295: 37-43
• 16 Hu F-Q, Ren G-F, Yuan H. et al. Shell cross-linked stearic acid grafted chitosan oligosaccharide self-aggregated micelles for controlled release of paclitaxel. Colloids and Surfaces B: Biointerfaces 2006; 50: 97-103
• 17 Kong M, Zuo Y, Wang M. et al. Simply constructed chitosan nanocarriers with precise spatiotemporal control for efficient intracellular drug delivery. Carbohydrate Polymers 2017; 169: 341-350
• 18 Wu D-Y, Ma Y, Hou X-S. et al. Co-delivery of antineoplastic and protein drugs by chitosan nanocapsules for a collaborative tumor treatment. Carbohydrate polymers 2017; 157: 1470-1478
• 19 Shaabani A, Nosrati H, Seyyedhamzeh M. Cellulose@ Fe2O3 nanoparticle composites: Magnetically recyclable nanocatalyst for the synthesis of 3-aminoimidazo [1, 2-a] pyridines. Research on Chemical Intermediates 2015; 41: 3719-3727
• 20 Shaabani A, Nosrati H, Hezarkhani Z. et al. One-pot oxidative groebke–blackburn–bienayme reaction of alcohols: Using bio-supported and magnetically recyclable Fe2O3@ cellulose and Fe2O3@ cellulose–SO3H nanocomposites for the synthesis of 3-aminoimidazo [1, 2-a] pyridines. Monatshefte für Chemie-Chemical Monthly 2018; 149: 1459-1467
• 21 Chen W, Shen H, Li X. et al. Synthesis of immunomagnetic nanoparticles and their application in the separation and purification of CD34+hematopoietic stem cells. Applied Surface Science 2006; 253: 1762-1769
• 22 Liu X, Xing J, Guan Y. et al. Synthesis of amino-silane modified superparamagnetic silica supports and their use for protein immobilization,. colloids and surfaces A: Physicochemical and engineering aspects 2004; 238: 127-131
• 23 Zhu L, Ma J, Jia N. et al. Chitosan-coated magnetic nanoparticles as carriers of 5-fluorouracil: Preparation, characterization and cytotoxicity studies,. colloids and surfaces B: Biointerfaces 2009; 68: 1-6
• 24 Salerno A, Verdolotti L, Raucci M et al. Hybrid gelatin-based porous materials with a tunable multiscale morphology for tissue engineering and drug delivery. European Polymer Journal 2017
• 25 Ramya JR, Arul KT, Sathiamurthi P. et al. Enhanced magnetic behaviour and cell proliferation of gamma irradiated dual metal ions co-doped hydroxyapatite–poly (methyl methacrylate) composite films. Reactive and Functional Polymers 2018; 123: 34-43
• 26 Yoon TJ, Kim JS, Kim BG. et al. Multifunctional nanoparticles possessing a “magnetic motor effect” for drug or gene delivery. Angewandte Chemie 2005; 117: 1092-1095
• 27 Tarantash M, Nosrati H, Kheiri Manjili H. et al. Preparation, characterization and in vitro anticancer activity of paclitaxel conjugated magnetic nanoparticles. Drug development and industrial pharmacy 2018; 44: 1895-1903
• 28 Max J-J, Chapados C. Infrared spectroscopy of aqueous carboxylic acids: Comparison between different acids and their salts. The Journal of Physical Chemistry A 2004; 108: 3324-3337
• 29 Yallapu MM, Othman SF, Curtis ET. et al. Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications. International journal of nanomedicine 2012; 7: 1761
• 30 Li M, Neoh K-G, Wang R. et al. Methotrexate-conjugated and hyperbranched polyglycerol-grafted Fe₃O₄ magnetic nanoparticles for targeted anticancer effects. European Journal of Pharmaceutical Sciences 2013; 48: 111-120