ВСТАНОВЛЕННЯ УМОВ СТАБІЛІЗАЦІЇ МАГНІТНИХ НАНОЧАСТИНОК У СКЛАДІ СИСТЕМ МАГНІТОКЕРОВАНОГО ТАРГЕТІНГУ ЛІКАРСЬКИХ РЕЧОВИН
Authors: Ведерникова І. О. 
Published: September 2015

<p><strong>STUDYING THE CONDITIONS OF STABILIZATION OF MAGNETIC NANOPARTICLES IN A MAGNETIC TARGETING DRUGS SYSTEM</strong></p><p><strong> </strong></p><p><strong>I.O. Vedernikova</strong></p><p>National University of Pharmacy, Kharkov</p><p> </p><p><strong>Abstract: </strong>aggregation and sedimentation stability of water-based magnetite systems were studying. Stable dispersion system PEO/magnetite without the use of surfactants was developed. Surface modification of the magnetic particles using a solution of HCl and polyelectrolytes (pectin, sodium oleate) increases the stability of the systems by 60%. Using IR-spectroscopy the chemical interaction of SAS molecules with the surface layer of magnetite iron cations was determined.</p><p><strong>Key words: </strong>magnetite nanoparticles, stabilization, magnetically drug delivery systems.</p><p> </p><p><strong>Introduction. </strong>Recently, there have been very popular works on the design and analysis of magnetically drug delivery systems to "target-organ" (magnetic targeting) under the influence of an external magnetic field [1-4]. The conditions of stabilization of magnetic nanoparticles in such systems can be defined by structural - rheological properties of the dispersion medium. In the case of using of polar dispersion unstructured environment (such as water) stability of the systems can be achieved using electrostatic and steric stabilization factors. In a viscous base the stabilization of magnet particles is possible without using of surfactant, due to the forces of viscous resistance of the dispersion medium.</p><p>For the such systems the nature of interaction of adsorbent-adsorbat between the particles of magnetic phase and surfactant molecules (or environment) should be determined, that affects the state of the surface and subsurface layers of magnetic nanoparticles and thus on their magnetic properties and the magnitude of the magnetic interparticle interaction [5-8].</p><p>Considering the importance of these samples for biomedical applications and the fact that most applications require the use of this material in the form of aqueous colloidal suspensions, it is worth studying the magnetite surface chemistry and the stability of the particles in water.</p><p>The aim of this work is to investigate the aggregation and sedimentation stability of the synthesized magnetite particles in v<em>arious rheological</em> dispersion medium, to determine the interaction of "adsorbent - adsorbat" between the particles of magnetic phase and the stabilizer molecules.</p><p><strong>Materials and Methods. </strong>The<strong> </strong>samples of magnetite nanoparticles suspended in water-based (surfactant were sodium oleate, 0.5% aqueous solution of hydrochloric acid, 3% aqueous solution of pectin) and polyethylene-based (PEO1500: PEO400 8: 2) were investigated. Synthesis of magnetite particles was performed by chemical coprecipitation: average particle diameter &lt;d&gt; = 20 nm, X-ray density ρ = 5.2 g∙cm<sup>-3</sup>.</p><p>The value of ξ-potential was determined experimentally by means of moving boundaries technic. Sedimentation stability of dispersions was studied using the <em>changes</em> in the <em>suspension optical</em> properties, LMF – 72M <em>photometer </em>was used.</p><p>Infrared spectra of the magnetite nanoparticles and systems were recorded between 4000 and 400 cm<sup>−1</sup> in order to confirm the nature of the coating and its bonding to the surface. Samples were prepared by diluting the samples in KBr at 2% by weight and pressing into a pellet</p><p><strong>Results and discussion. </strong>The obtained values of electrokinetic potential of research systems and sedimentation results are presented in Table 1. It was found relatively high values of electrokinetic ξ-potential for all experimental systems. Adding the stabilizer led to an increase in potential values on average by 45% and sedimentation stability constants at 60%. The efficiency of the electrolyte can be explained with the formation of the electrical double layer on the surface of magnetite particles.</p><p> </p><p align="center"><strong>Table 1. </strong>Electrokinetic potential of dispersion, average size and</p><p align="center">aggregation degree of particles of magnetic phase<strong></strong></p><table border="1" cellspacing="0" cellpadding="0" align="left"><tbody><tr><td rowspan="2" valign="top"><p align="center">№ sample</p></td><td rowspan="2" valign="top"><p align="center">The composition of dispersed systems</p></td><td rowspan="2" valign="top"><p align="center">Value ξ-potential,</p><p align="center">10<sup>2</sup> V</p></td><td colspan="3" valign="top"><p align="center">Average size of particles, nm / degree of aggregation, %</p></td></tr><tr><td valign="top"><p align="center">1 day</p></td><td valign="top"><p align="center">7 days</p></td><td valign="top"><p align="center">60 days</p></td></tr><tr><td valign="top"><p align="center">1</p></td><td valign="top"><p align="center">magnetite/water</p></td><td valign="top"><p align="center">4.28</p></td><td valign="top"><p align="center">120/40</p></td><td valign="top"><p align="center">120/40</p></td><td valign="top"><p align="center">120/40</p></td></tr><tr><td valign="top"><p align="center">2</p></td><td valign="top"><p align="center">magnetite/5% solution of  HCl/water</p></td><td valign="top"><p align="center">6.28</p></td><td valign="top"><p align="center">60/10</p></td><td valign="top"><p align="center">60/10</p></td><td valign="top"><p align="center">60/10</p></td></tr><tr><td valign="top"><p align="center">3</p></td><td valign="top"><p align="center">magnetite/sodium oleate /water</p></td><td valign="top"><p align="center">6.95</p></td><td valign="top"><p align="center">80/20</p></td><td valign="top"><p align="center">80/20</p></td><td valign="top"><p align="center">80/20</p></td></tr><tr><td valign="top"><p align="center">4</p></td><td valign="top"><p align="center">magnetite/3% solution of pectin/water</p></td><td valign="top"><p align="center">7.08</p></td><td valign="top"><p align="center">80/20</p></td><td valign="top"><p align="center">80/20</p></td><td valign="top"><p align="center">80/20</p></td></tr></tbody></table><p>                                                                                                                               </p><p>The suspension with the pectin solution (anionic polyelectrolyte) seems to provide <em>the best properties</em>. On the surface of the micelle core (magnetite particles) the anions of D-galacturonic acid (the main component of pectin) were adsorbed. This increases the stability of the dispersion system and facilitates the spatial structuring of colloidal particles (granules).</p><p>For the magnetite particles in the PEO-based dispersed systems using Rebinder’s effect and Deryagin’s rule an algorithm was developed. It was founded, that the disperse system PEO/magnetite has the necessary <em>condition</em> for <em>sedimentation stability</em>: low sedimentation rate of the magnetic phase (2.15·10<sup>-9</sup> cm·s<sup>-1</sup>) and high value of the measures of kinetic stability (45·10<sup>5</sup>).</p><p>The type of the interaction between the stabilizer molecules and the magnetite particles was determined using IR-spectra analysis (Fig. 1).</p><p>In the resulting spectra of the samples (fig. 1 <strong><em>а</em></strong><strong><em>,</em></strong> <strong><em>b</em></strong>), a band exhibits in the range 3200-3600 cm<sup>-1. A broad absorption band of medium intensity in <strong><em>a</em></strong> spectrum, and the high intensity in <strong><em>b</em></strong> spectrum (Fig. 1), are associated with – OH groups </sup>stretching.</p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p align="center"><strong>Fig. 1.</strong> IR - spectra of synthetic magnetite nanoparticles (a)</p><p align="center">magnetic system magnetite/sodium oleate/water (b)</p><p> </p><p><em>The bands</em> in FTIR <em>spectrum of magnetic system (f</em>ig. 1, <strong><em>b</em></strong>) show  the existence of the hydroxide groups in the water and sodium oleate (region 2950 – 2850 cm<sup>-1</sup>), С=О vibrations (1712 cm<sup>-1</sup>), bending of С=С (1457 cm<sup>-1</sup> and 1377 cm<sup>-1</sup>). The peaks at 2953 and 2854 cm<sup>-1 </sup>are attributed to the rocking –СН<sub>2</sub> and –СН<sub>3</sub>. The peaks at 1457 cm<sup>-1</sup> and 1377 cm<sup>-1</sup> – bending of –CH  vibrations.</p><p>Infrared studies indicated the presence of a strong absorption line in pure magnetite <em>(f</em>ig. 1, <strong><em>a</em></strong>) located at 570 cm<sup>−1 </sup>which was attributed to the stretching vibration of Fe-O in tetrahedral sites [5-10].  Shifting the absorption maximum of this bond and its splitting (587 cm<sup>-1</sup> and 634 cm<sup>-1</sup> (Fig. 1<strong><em>b</em></strong>)) may be attributed to the influence of surfactant molecules, with their interference in the subsurface layer of magnetic nanoparticles and chemical bonding with iron cations.</p><p> Chemical bonding of the surface atoms of the magnetic particles with the stabilizer molecules reduces the "magnetic size" of the particles. Besides excessive local concentration of the stabilizer molecules on the surface of the particles forms the paramagnetic layer. Thus, on the one hand due the presence of surfactant prevents aggregation of the particles in the medium with low structural and mechanical resistance on the other, the use of stabilizer (oleic acid and its salts) leads to decrease in the magnetic properties of such a system, that should be considered.</p><p><strong>Conclusions. </strong>Electrophoretic mobility data were transformed to zeta potential values, which are related to the surface charge density and depend on the oxide composition, crystalline form, size and surface characteristics. Under the studying the properties of water-based magnetite dispersion it was founded that the use of a solution of hydrochloric acid, sodium oleate and pectin as stabilizers leads to increased stability of disperse systems (and z-potential value) and promotes spatial structuring of colloidal particles. 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