Journal of the Korean Physical Society, Vol. 52, No. 5, May 2008, pp.

1332$1335

Size Controlled Magnetite Nanoparticles and Their Drug Loading Ability
C. V.

Thach,

N. H.

Hai£

and N.

Chau

Center for Materials Science, Hanoi University of Science, 334 Nguyen Trai, Hanoi, Vietnam

(Received 15 July 2007) Magnetite nanoparticles (MNPs) were synthesized by using coprecipitation method with a reaction between the FeCl2 /FeCl3 solution and the ammonia water. The size of the MNPs could be controlled from 10.0 to 14.6 nm by changing the concentration of the solutes. The particles were superparamagnetic at room temperature. The saturation magnetization of the MNPs increased with increasing concentration of reactants. The magnetite nanoparticles were coated with a single layer of oleic acid (OA) to have a hydrophobic surface or with a double layer of oleic acid/sodium dodecyl sulfate (OA/SDS) to have hydrophilic surface. The coated particles could be dispersed in n-Hexane or water. The OA/SDS-coated nanoparticles were used to load an antibiotic drug, chloramphenicol (Cm). Three weight percent of Cm could be loaded onto the OA/SDS coated nanoparticles, which is much higher than amount that can be loaded using the traditional drug loading method.
PACS numbers: 75.50.Mm, 78.67.Bf, 87.83.+a Keywords: Magnetic nanoparticles, Magnetic uids, Magnetite, Drug delivery, Biophysics
I. INTRODUCTION

Magnetic uids consisting of magnetic nanoparticles are the subject of many recent studies, especially in biological applications such as cell separation and sorting, magnetic drug delivery and magnetic resonance imaging [1,2]. On a scale smaller than a critical length, the ferromagnetic behavior of materials disappears and changes to a superparamagnetic (SP) state. The critical length in this case is on the order of few tens of nm at which the thermal agitation dominates the ferromagnetic order. Superparamagnetic materials show strong magnetic properties under an applied magnetic

but a nonmagnetic behavior when the .eld.

82 g of FeCl3 .25 M (0. environmental stability.15.25) to investigate the in uence of the concentration of the reactants on the size and the magnetic properties of synthesized MNPs. OH  was adjusted accordingly). was changed from 0. EXPERIMENTS nhhai@vnu. the particle size was successfully controlled by changing the concentration of reactants. 0.05. simple preparation and cost e ectiveness.4H2 O (molar concentration c = 0.1. c (the concentration of Fe3+ .01. black precipitates of magnetite were washed . biological compatibility. The drug loading ability of MNPs is also presented.002 M to 0. 0. The superparamagnetic state is very important in many in-vivo biological applications because it prevents aggregation in the bloodstream. This paper reports the preparation of MNPs by using a coprecipitation method and the use of their superparamagnetism and their large surface areas in applications of drug delivery. ferromagnetic behavior is required [2]. Coprecipitation is a simple method to synthesize MNPs. However. 0. 3.eld is removed. 0.1 M) and 10. In our studies. but the particle size is dicult to control.edu. 0. 0. Magnetite nanoparticles were then functionalized to have £ E-mail: hydrophobic and hydrophilic surfaces to disperse in oil and water and to aim magnetic uids.vn.6H2 O were dissolved in 200 ml of distilled water.005. In a typical reaction. in some cases such as hyperthermia. II. In our study.002. An 18 ml solution of NH4 OH 25 % diluted to 100 ml by water. Magnetite Fe3 O4 NPs are the most commonly used magnetic material due to its high saturation magnetization Ms (90 emu/g). 0. After the reaction. 0. Fax: +84-4-858-9496 -1332- Magnetite nanoparticles were synthesized by coprecipitating a Fe2+ /Fe3+ mixed solution (the molar ratio Fe2+ : Fe3+ = 1 : 2) with a NH4 OH solution in air [3].98 g of FeCl2 . was then added to the Fe2+ /Fe3+ solution at a rate of one drop per second at room temperature with constant stirring.02. the concentration of Fe2+ .2.

ve times by using distilled water and magnetic decantation to remove all the soluble substances.5 g of MNPs in 20 ml of water were then vigorously mixed with 10 ml of oleic acid (OA. CAS number: 112-80-1) in order to coat the MNPs with a single surfactant layer of OA (denoted as OA-coated nanoparticles) and to disperse them into a non-polar solvent n-Hexane. 0. the OA-coated nanoparticles in 20 ml n-Hexane were . For dispersing in water. 9-Octadecenoic acid C18 H34 O2 . The excess OA was washed o three times by using nHexane and magnetic decantation.

mixed with 40 ml of an aqueous solution containing 1 g of sodium dodecyl sulfate (SDS.05 M and = 0. 96 mg of Chloramphenicol (Cm) was dissolved in 2.Size Controlled Magnetite Nanoparticles and Their¡ ¡ ¡ { C. The excess SDS was washed o three times by using water with the help of magnetic decantation. Thach et al. V. The unloaded Cm was washed o .5 ml of ethanol and then diluted to 10 ml by using distilled water. To load antibiotic into the SDS/OA nanoparticles. TEM images of the samples with c = 0. 2. XRD pattern of a typical sample with c = 0. The powder di raction intensities of Fe3 O4 (pdf: 1-1111) are presented by the bars. 1. Then. the obtained Cm solution was vigorously mixed with 100 mg of OA/SDS-coated MNPs in 20 ml of water for 15 hours. -1333- c Fig.25 M. Fig. CAS number: 151-21-3) to obtain double layer OA/SDS nanoparticles (denoted as SDS/OA nanoparticles).2 M. Sodium lauryl sulfate C12 H25 OSO3 Na.

Magnetic properties were measured by using a DMS 880 vibrating sample magnetometer. Fourier Transformed Infrared (FTIR) Spectra were recorded in the transmission mode on a Nicolet Impact 410 spectrometer. The particles sized were determined by using a JEOL JEM 1010 transmission electron microscope (TEM). The achieved sample was then stored at low temperature (5  C) to limit the di usion of Cm from OA/SDS coated MNPs. III. The thermogravimetric analysis (TGA) was carried out by using a SDT 2960 TA Instrument. A cooper grid was dipped in a solution containing OA-coated NPs and then dried before being submitting for TEM. RESULTS AND DISCUSSION XRD patterns having all the characteristic peaks of magnetite Fe3 O4 con. The structural analysis of a dried powder of MNPs was conducted by using a D5005 X-ray di ractometer.ve times by distilled water with the aid of magnetic decantation.

the nuclei so obtained are allowed to grow uniformly by di usion of solutes from the solution and/or aggregation of other nuclei to their surface until the . All peaks are broadened due to the small sizes of nanoparticles. Then.2 M and re ections of standard Fe3 O4 powder are shown in Figure 1. The XRD results do not show the presence of impurities or of other phases. The mechanism of MNP formation is understood as a short single burst of nucleation that occurs when the concentration of constituent species reaches critical supersaturation.rmed that all samples were magnetite with the inverse spinel structure as in the case of the bulk sample. Typical XRD patterns of a sample with c = 0.

all samples ex- . When the solution is diluted (c = 0. but the clusters of NPs can be explained by the drying process in the preparation for TEM measurements. Particles are spherical with a diameter.6 nm if c is greater than 0. However. resulting in a limited growth process for the particles. For a small particle size of about 10 nm. The particle size can be even greater than 14. which is unexpected in further applications in drug delivery.25 M. a dilution of the solution is needed.05 M).25 M are shown in Figure 2. Changing the concentration of Fe2+ can change the particle size. the di usion of solutes is limited.05 M because 10 nm is considered to be the smallest particle size that can be obtained by using a conventional coprecipitation process. the growth process happens much more strongly. Sizes of 10 { 100 nm can be made by using this technique.nal size is attained [4]. but we don't need to decrease c lower than 0. which creates a particle size of 14:6 ¦ 3:2 nm. the size (d) can be controlled by using the pH and the ionic strength [5].25 M). As the concentration increases (c = 0. Nanoparticles should be well separated due to the OA coating layer. Transmission electron microscope images of two typical samples with c = 0. Owing to the particle size being smaller than the critical length (superparamagnetic radius). A smaller size is dicult to obtain.05 M and c = 0. of 10:0 ¦ 2:8 nm. particles of greater sizes may lose their superparamagnetic behavior. as determined from the TEM image. In conventional coprecipitation.

Dependence of the saturation magnetization on the concentration and a typical magnetization curve of the sample with c = 0. 3. hibit superparamagnetic properties at room temperature. May 2008 Fig.-1334- Journal of the Korean Physical Society. No. with their saturation magnetizations depending on the concentration as shown in Figure 3. 5. The magnetization curve of a typical sample with c = 0. 52. Vol.2 M (the inset).2 M (the inset in Figure 3) shows no remanence (the remained magnetic magnetization after removing the applied magnetic .

eld) and coercivity (the applied magnetic .

The OA/SDScoated NPs shows two mass losses: 3 % in the range of 200  C { 300  C (OA evaporation dominated) and 5 % Fig. This fact is also supported by the FTIR spectra. With the presence of SDS molecules. This indicates chemisorption of OA hydrophilic heads at the NP surface and of hydrophobic tails of the hydrocarbon chain at the carrier liquid (the lower left in Figure 4). the greater the particle size and/or the lower the oxidation. the higher the concentration.eld required to demagnetize the MNPs). which make the OA molecule more dicult to evaporate. in the range of 300  C { 400  C. respectively. The black zigzag curves represent the hydrophobic tails. which results in unexpected properties. the C=O band (1280 cm 1 ). That value is smaller than that of bulk samples. In both cases. Bare MNPs can be quickly aggregated to make clusters of particles. reveal the absence of the all peaks for C=O and O-H whereas two peaks of the CH2 stretching modes are still present. the hydrophobic tail of this molecule will tend inward to the particle. suggesting binding of the carboxylic group of OA to the iron oxide nanoparticles [6]. the O-H inplane band (1460 cm 1 ) and O-H out-of-plane band (910 cm 1 ). which can be explained by the evaporation of OA. 2932 cm 1 ). this higher range suggests bonds between OA and the MNP surface. making the saturation magnetization higher. 4. however. TGA measurements of the bare MNPs and of the OA-coated and the OA/SDS-coated MNPs were performed (not shown). This problem was solved by coating MNPs with a single surfactant layer (OA) or with a double surfactant layer (OA/SDS). there are absorbance peaks of the C=O stretch dimer H-bonded (1707 cm 1 ). the O-H stretch dimer H-bonded (broad peak at 3000 cm 1 ). In the FTIR spectra of pure OA. The inward and the outward circles represent the hydrophilic heads of the OA and the SDS surfactants. which is attributed to the core-shell structure of the particles and the possible oxidation by the oxygen di using into the solutes. the symmetric and asymmetric CH2 stretching modes (2861 cm 1 . which can be ascribed to the remaining water trapped in the samples. OA-coated MNPs and pure OA (upper) and a schematic illustration (lower left) of a single layer OA-coated and (lower right) of a double layer OA/SDS-coated MNPs. The saturation magnetization increases with the increasing concentration of solutes and reaches 74 emu/g. OA-coated MNPs and OA are shown in Figure 4. However. The spectra of OA-coated NPs. as shown in Figure 4 (the . FTIR measurements of bare MNPs. FTIR spectrum of bare MNPs. The bare MNPs show a small mass loss of 1 % over the whole range of temperature from room tempearture to 500  C. when compared with the boiling temperature of OA 150  C { 250  C. OA-coated NPs show a loss of 7 % in mass in the range of 220  C { 420  C.

The project is . we claim that the loaded Cm occupies 3 % of the mass. Chloramphenicol is loaded into the space between the two surfactant layers thanks to the hydrophobic anity and contributes 3 % of the mass of whole system. From the total mass loss of the two samples. The amount of the loaded Cm was estimated by using TGA measurements on the OA/SDS-coated MNPs and the Cm-loaded OA/SDScoated MNPs (Figure 5). -1335IV. because it is applicable for all the hydrophobic drugs frequently used in pharmacy. which are normally less than 1 %.Size Controlled Magnetite Nanoparticles and Their¡ ¡ ¡ { C. 5. Temperature dependence of the normalized mass of Cm-loaded OA/SDS-coated MNPs and OA/SDS-coated MNPs. creating a double layer OA/SDS-coated MNPs double layer occupies 8 % of mass. SDS. Another surfactant. It is reasonable to expect our system to be a good candidate for applications in magnetic drug delivery. Fig. V. CONCLUSIONS Using a coprecipitation method. surrounds the OAcoated MNPs. but very large in comparison with that obtained by using traditional methods. We use this feature for drug loading. respectively. Thach et al. The mechanism of this process is the hydrophobic anity [6]. That. This value is smaller than recently achieved result [6]. a hydrophobic antibiotic drug. OA molecules bond by chemisorption with MNPs and contribute 7 % of the mass of OA-coated MNPs. we can synthesize superparamagnetic MNPs with their size (d) being controlled by changing the concentration of reactants (c): d = 10:0 ¦ 2:8 nm for c = 0. The mechanism of loading Cm into OA/SDS MNPs is quite simple. but versatile. Cm was successfully loaded into OA/SDS-coated MNPs is also evident in the antibiotic behavior test of Cm-loaded OA/SDS-coated MNPs [7]. ACKNOWLEDGMENTS lower right) and leave a hydrophobic space between two layers.25 M. The saturation magnetization of MNPs increases with increasing concentration and can reach 74 emu/g. was loaded into the hydrophobic space between the two surfactant layers. 10 % and 13 %. Chloramphenicol (Cm).05 M and d = 14:6 ¦ 3:2 nm for c = 0. as presented in the experiment section.

[7] N. V. Korean Phys. J. J. J. A. [2] Q. B. Dobson. Phan and N. Gonzalez-Carreno and C. J. 36. J. 2. J. Jain. [3] P. LesliePelecky and V. S. . 194 (2005). Labhasetwar. Beckman. C. Hai. T.. R182 (2003). L. S. Chau. edited by D. J.nancially supported by the Vietnamese Fundamental Research Program for Natural Sciences (Project 406506). Sellmyer and R. Morales. J. Adelman. Pankkhurst. in this issue. Nguyen. 943 (1999). Ellis and G. C. Morales. New York.Pharm. Thach. H. T. Phys. Phys. in Advanced Magnetic Nanostructures. L. Chem. J. D: Appl. S. Skomski (Kluwer. Khuat. Jr. A. Kraus. [5] J. A. Connolly. Serna. K. Sahoo. Mol. Leslie-Pelecky. N. Tartaj. P. Jolivet. T. Campbell. R167 (2003). Berger. N. D. T. Soc. K. V. P. M. M. H. 36. D. [4] P. Phys. K. New York.. B. REFERENCES [1] D. Labhasetwar and R. Veintemillas-Verdaguer. Phys. 2000). 76. Lisensky. N. 2005). Edu. S. Jones and J. [6] T. K. Nanobiomagnetics. V. A. Metal Oxide Chemistry and Synthesis: From Solutions to Solid State (Willey. D: Appl.