WO2008069561A1

WO2008069561A1 - Metal oxide hollow nanocapsule and a method for preparing the same

Info

Publication number: WO2008069561A1
Application number: PCT/KR2007/006269
Authority: WO
Inventors: Taeghwan Hyeon; Yuanzhe Piao; Jaeyun Kim
Original assignee: Seoul National University Industry Foundation
Priority date: 2006-12-05
Filing date: 2007-12-05
Publication date: 2008-06-12
Also published as: KR100846839B1; KR20080051285A

Abstract

The present invention relates to a metal oxide hollow nanocapsule which is able to disperse well in aqueous systems and a method for preparing thereof. The method for preparing the iron oxide hollow nanocapsules according to the present invention is characterized by dispersing metal oxyhydroxide in an aqueous solution and coating said metal oxyhydroxide with silica coating layer and administering heat treatment to form a metal oxide layer around the internal hollow space of the silica coating layer and removing said silica to obtain the metal oxide hollow nanocapsule. The iron oxide hollow nanoparticles prepared by the method of the present invention do not only have superior dispers ability in aqueous solutions and uniform size distribution, and said iron oxide hollow nanocapsule can also carry physiologically active materials within the hollow space of said nanocapsule. In addition, the iron oxide hollow nanocapsules of the present invention have a large surface area of at least 100 m2/g and narrow mesopore size distribution which allows physiologically active material carrying capability which brings great expectations for a wide range of industrial uses such as drug delivery vehicles for biomedical applications, gas sensors, lithium ion batteries, etc.

Description

METAL OXIDE HOLLOW NONOCAPSULE AND A METHOD

FOR PREPARING THE SAME

Technical Field

[1] The present invention relates to a metal oxide hollow nanocapsule which is able to disperse well in aqueous systems and a method for preparing thereof. Background Art

[2] Due to the wide range of possible applications for iron oxide nano materials, research on this type of nanoparticle is capturing the interest of many. For use in the biomedical field, the most essential factor of the iron oxide nanomaterial is the uniformity in size, and good dispersion and stability in a biological medium. Currently, most commercialized nanoparticles are commonly synthesized in water or obtained through a synthesis process in a gaseous form. However, it is difficult in the above process to obtain uniform nanoparticles, and the nanoparticles obtained thereof have a low degree of crystallinity. Compared to nanoparticles which are synthesized in water ,researchers recently have been developing methods to prepare high quality, namely, uniformly sized and crystalline oxide nanoparticles in an organic solvent, [a) Y.S Kang, S. Risbud, J. F. Rabolt, P. Stroeve, Chem. Mater. 1996, 8, 2209. b) W. W. Yu, J. C. Falkner, C. T. Yavuz, V. L. Colvin, Chem. Commun. 2004, c) S. Sun, H. Zeng, J. Am. Chem. Soc. 2002, 124, 8204. d) T. Hyeon, S. S. Lee, J. Park, Y. Chung, H. B. Na, J. Am. Chem. Soc. 2001, 123, 12798. e) J. Park, K. An, Y. Hwang, J.-G. Park, H.-J. Non, J.- Y Kim, J.-H. Park, N.-M. Hwang, T. Hyeon, Nature Mater. 2004, 3, 891. f) J. Park, E. Lee, N.-M. Hwang, M. Kang, S. C. Kim, Y. Hwang, J.-G. Park, H.-J. Noh, J. -Y. Kim, J.-H. Park, T. Hyeon, Angew. Chem. Int. Ed. 2005, 44, 2872.]. However, in these cases in which nanoparticles are synthesized in organic solvents, because the uniformity and size of the nanoparticle are regulated through the stabilization process through the surfactant, and due to the hydrophobic carbon chains of the surfactant, the resulting nanoparticles disperse in hydrophobic solvents but do not disperse in hy- drophilic water and there is no apparent sufficient stability in the water. This presents a problem for applications in the biomedical field because the hydrophobic characteristic of the nanoparticle disrupts the stability in water. Therefore, because the iron oxide nanoparticles must have uniform size range for these applicable fields, there is much research towards a technique for large scale production of iron oxide nanoparticles which have superior dispersibility in aqueous systems.

[3] In addition, in order to improve performance in the wide range of applications, it is important to synthesis empty, namely hollow type nanomaterials. A conventional technique for the synthesis method of hollow iron oxide nanomaterial was published in a recent journal [Jun Chen et. al., ¹Ci-Fe₂O₃ nanotubes in gas sensor and lithium- ion battery applications', Adv. Mater. 17, 582(2005)]. However, because of various limitations of essential factors, synthesis on a large scale is not easy and there are difficulties with size regulation as well as other difficult problems. In addition, a recent report discloses the possible synthesis of hollow metal oxide nanoparticles using an autoclave. [Chun-Hua Yan et. al., 'Single-crystalline iron oxide nanotubes', Angew. Chem. Int. Ed. 44, 4328(2005). Lu Liu et. al., ;'Surfactant-assisted synthesis of Ci-Fe₂O₃ nanotubes and nanorods with shape-dependent magnetic properties', J. Phys. Chem. B 110, 15218(2006).]

[4] However, said method is not economical in respect to the costs of the manufacturing equipment due to the autoclave. The iron oxide nanomaterials produced by said method have limited applicability to the biomedical field since said iron oxide nanomaterials are of tubular form with a length of 300nm or have surfactants at the surface of said nanoparticles when produced with surfactants. The report does not mention the water-dispersability of said nanomaterials.

[5] Furthermore, Yi Xie et al. (Thermally stable hematite hollow nanowires', Inorg.

Chem. 2004, 43, 6540.) discloses the manufacture of hollow metal oxide nano- structures, wherein β-FeOOH undergoes pryolysis in a vacuum for a method of producing tubular metal oxide nano-structures. However, the diameters of the produced tubes are relatively as large as 50nm and thus, the surface area of said tubes are as small as 19.06m²/g. Also, Xi Yei et. al. does not disclose the water-dispersability of said nanotubes. In addition, the method for preparing iron oxide nanotubes disclosed by Chongwu Zhou et. al. ('Single crystalline magnetite nanotubes', J. Am. Chem. Soc. 2005, 127, 6.) is shown in Fig. 1. With reference to Fig. 1, a MgO nanorod is used as a template and is coated epitaxially with Fe₃O₄, and then MgO, the core material, is removed. The nanotubes obtained from the above method have limited application in the biomedical field such as drug delivery etc. due to their sizes which are up to micrometers.

[6] In addition, it is an essential factor for application in the biomedical field that nanomaterials containing iron oxide be dispersable in water, therefore, research on the water-dispersibility of nanomaterials has recently attracted more attention and various research has been conducted [ a] Y. Wang, J. Wong, F.X. Teng, X.Z. Lin, H. Yang, Nano Lett. 2003, 3, 1555. b) Z. Li, H. Chen, H. Bao, M. Gao, Chem. Mater. 2004, 16, 1391. c) T. Pellegrino, L. Manna, S. Kudera, T. Liedl, D. Koktysh, A. L. Rogach, S. Keller, J. Raldler, G. Natile, WJ. Parak, Nano Lett. 2004, 4, 703.]. However, research on the water-dispersable hollow iron oxide nanomaterials have been very insufficient.

[7] Furthermore, a prior technique related to the synthesis of iron oxide nanomaterials is disclosed in Japanese patent no. 1984-197506 and 1989-212231, wherein a synthesis method is laid open wherein silicate is mixed in ferric oxyhydroxide and then undergoes heat treatment for the synthesis of iron oxide particulate materials. However, in the said methods, the silicate is simply mixed in ferric oxyhydroxide (α-FeOOH or γ-FeOOH) to maintain cohesion between the metal oxide nanomaterials, and because it is difficult for the silicate coating layer to form uniformly, it cannot be applied for the synthesis of uniformly shaped hollow metal oxide nanoparticles.

[8] As mentioned above, the traditional technique involves the use of specific equipment such as an autoclave in the manufacturing method, which is not economical in view of the equipment costs for manufacture, and thus is not only unsuitable for large-scale production, but there are also limitations in the applicability in the biomedical field due to the size of the synthesized nanomaterials, and furthermore, there is no progress in the research for dispersion in aqueous systems.

[9] Consequently, a specific uniform size range for biomedical applications and the development of a new form of metal oxide hollow nanoparticles with superior biomedical applicability and a technique for manufacturing metal oxide hollow nanocapsules with superior dispersability is required. Disclosure of Invention Technical Problem

[10] An object of the present invention is to provide a method for preparing metal oxide hollow nanocapsules with aqueous dispersablity which has superior uniform size distribution.

[11] Another object of the present invention is to provide a method for preparing metal oxide hollow nanocapsules with aqueous dispersablity and superior uniform size distribution without the required use of an autoclave and which is economically applicable for large-scale production.

[12] Yet another object of the present invention is to provide a metal oxide hollow nanocapsule with superior dispersion in aqueous systems and suitable size and shape for applications in the biomedical field.

[13] Yet another object of the present invention is to provide an iron oxide hollow nanocapsule in which said metal oxide hollow nanocapsule acts as a delivery vehicle which carries physiologically active materials inside the nanocapsule. Technical Solution

[14] After dispersing metal oxyhyroxide particles in an aqueous solution and forming a silica coating layer around said metal oxyhydroxide particle, heat treatment was administered whereupon the present inventors discovered the formation of a hollow metal oxide layer inside the hollow space of the silica coating layer, which led to the achievement of the present invention.

[15] Accordingly, the present invention provides a method for preparing metal oxide hollow nanocapsules, which comprises:

[16] a) dispersing metal oxyhydroxide particles in a water and alcohol mixture solution to prepare a metal oxyhydroxide dispersion solution;

[17] b) adding a silica precursor agent into the metal and alcohol mixture solution for sol- gel reaction to form the silica coating layer around the metal oxide particle;

[18] c) administering heat treatment to make the silica coating layered metal oxide hollow nanocapsules; and

[19] d) removing said silica coating layer.

[20] The type of nanomaterial prepared by the method of the present invention depends on the metal of the metal oxyhydroxide used, thus, the metal oxyhydroxide used in the method of the present invention is selected from β-FeOOH (akaganeite), γ- AlOOH (boehmite), CoOOH (heterogenite), α-CrOOH (chromia aerogel), InOOH (indium oxyhydroxide), MnOOH (manganite), NiOOH (nickel oxyhydroxide), WOOH (tungsten oxyhydroxide), etc..

[21] According to the method for preparing metal oxide hollow nanoparticles of the present invention, particulate metal oxyhydroxide which is relatively unstable compared to stoichiometrically stable metal oxide is used to form a silica coating layer around the metal oxyhydroxide particle by sol-gel reaction, and then, via heat treatment, a layer of metal oxide made from metal oxyhydroxide, with uniform thickness is formed inside the silica coating layer with its shape maintained by the silica coating layer, and consequently the hollow space is formed with the metal oxide layer. Namely, during the heat treatment process the metal oxyhydroxide becomes pryolized and converts to a metal oxide which causes a decrease in volume, however, because the formed metal oxide adheres to the inner wall of the silica coating layer, it maintains the shape of the metal oxyhydroxide and thus the hollow nanocapsule is formed. The desirable thickness of said silica coating layer is 2nm to 200nm for the reason that if the outer shell is too thin then it is difficult to maintain its shape integrity. If the outer shell is too thick then subsequent removal thereof may be difficult. After said process, the metal oxide hollow nanocapsules can then be obtained by removing the silica coating layer. The metal oxide hollow nanocapsule prepared according to the present invention has the unique characteristics of regulated particle size uniformity and good dispersion in aqueous systems.

[22] In addition, the present invention provides metal oxide hollow nanocapsules prepared by method of the present invention

[23] Further, the present invention provides a metal oxide hollow nanocapsule which is made of hematite ((X-Fe₂O₃) or magnetite (Fe₃O₄). In accordance with the preferred em- bodiments of the present invention, said iron oxide hollow nanocapsules have the unique characteristics of a diameter of IOnm to 20nm and a length of 50nm to lOOnm wherein the shell thickness of spindle form is 5nm to 15nm. Further, said metal oxide hollow nanocapsule is able to carry physiologically active material and thus is suitable for use as a drug delivery vehicle.

[24] Hereinafter, the present invention will be described in more detail.

[25] Unless explicitly defined, all technical and scientific terms used in this invention have meanings commonly used by a person skilled in the art.

[26] In addition, any descriptions regarding the same techniques and operations as those in prior arts will be omitted.

[27] Accordingly, the present invention provides a method for preparing metal oxide hollow nanocapsules, which comprises:

[28] a) dispersing metal oxyhydroxide particles in a water and alcohol mixture solution to prepare a metal oxyhydroxide dispersion solution;

[29] b) adding a silica precursor agent into the metal and alcohol mixture solution for sol- gel reaction to form the silica coating layer around the metal oxide particle;

[30] c) administering heat treatment to make the silica coating layered metal oxide hollow nanocapsules; and

[31] d) removing said silica coating layer.

[32] The metal oxyhydroxide is selected from the group consisting of β-FeOOH

(akaganeite), γ-AlOOH (boehmite), CoOOH (heterogenite), α-CrOOH (chromia aerogel), InOOH (indium oxyhydroxide), MnOOH (manganite), NiOOH (nickel oxyhydroxide), WOOH (tungsten oxyhydroxide), etc.. Preferably β-FeOOH may be used to produce iron oxide hollow nanocapsules with high industrial applicability. More preferably, in the case when using the spindle form of β-FeOOH, since it can carry physiologically active materials it is suitable for use in the biomedical field.

[33] According to the present invention, for the method for preparing the spindle shape β-

FeOOH, ferric-ferrous salt was dissolved in distilled water followed by heating and stirring, wherein the preferred range of said heating temperature is between 60 to 90 degrees and the preferred stirring duration was between 6 to 72 hours. The β-FeOOH according to the method of the present invention has the advantage of having a uniform size distribution, and as a result, the uniform size distribution of hollow nanocapsules was able to be aquired.

[34] The particulate metal oxyhydroxide can be directly synthesized or can be used commercially. Said metal oxyhydroxide is dispersed in a mixture solution of water and alcohol, and then a silica precursor agent is added to the dispersed solution.

[35] Preferably, said alcohol is low alcohol since low alcohol has good miscibility with water and makes it easier to form the silica coating layer by sol-gel reaction of the silica precursor. When the silica precursor is added, in the presence of base catalyst, into the metal oxyhydroxide particle dispersed solution, the silica coating layer is formed around the metal oxyhydroxide particle by sol-gel reaction.

[36] The silica precursor used in the step of forming the silica coating layer is at least one selected from the group consisting of TEOS (tetraethyl orthosilicate), TMOS (tetramethyl orthosilicate), or TBOS (tetrabutyl orthosilicate).

[37] According to the method of the present invention, the basic catalysts used in the sol- gel reaction of step b) can be selected from the group consisting of ammonium hydroxide, potassium hydroxide, or sodium hydroxide. In said step b) the desirable thickness of said silica coating layer is 2nm to 200nm, for the reason that if the outer shell is too thin it is difficult to maintain its shape integrity, and if the outer shell is too thick then removal of the outer shell may be difficult. According to the present invention, the desirable temperature applied for heat treatment in step c) is between 400 to 1600⁰C, for the reason that in case the temperature of less than 400⁰C is applied in said heat treatment, the metal oxide does not form properly and thus crystallization of the metal oxide is difficult, and in the case that said temperature exceeds 1600⁰C, the silica coating will melt and cause extreme aggregation which will be a problem during removal. The method of the present invention may further comprise a step of reduction during or after said heat treatment stage, and the metal oxide may be changed into the other material via reduction. For example, hematite metal oxide may be converted to magnetite via reduction. In this case, hydrogen gas or NaBH₄ etc. may be used as the reducing agent.

[38] According to the method of the present invention, an inorganic base such as NaOH or KOH, or aqueous HF solution is used for the removal of the silica coating layer and it is much preferred to use supersonic wave treatment in combination with said inorganic base or hydrofluoric acid for the purpose of curtailing removal process time. After the silica coating layer is removed, iron oxide hollow nanocapsule is produced.

Advantageous Effects

[39] According to the present invention, hollow nanocapsules may be prepared by coating metal oxide oxyhydroxide with silica and using the heat treatment method. Thus the prepared hollow nanocapsules have the advantages of good dispersibility in aqueous systems and uniform size distribution. Further, compared to conventional techniques, the iron oxide hollow nanocapsules prepared by the method of the present invention is simple and can be produced economically on a large scale.

[40] In addition, the iron oxide hollow nanocapsules of the present invention have a large surface area of at least 100 m²/g and narrow mesopore size distribution which allows physiologically active material carrying capability which brings great expectations for a wide range of industrial uses such as drug delivery vehicles for biomedical applications, gas sensors, lithium ion batteries, etc. Brief Description of the Drawings

[41] Fig. 1 is a schematic diagram of the conventional method for preparing tubular iron oxide nanoparticles.

[42] Fig. 2 is a process diagram of the method of the present invention for preparing the iron oxide hollow nanoparticles

[43] Fig. 3(a) is an SEM (Scanning electron Microscopy) image of prepared β-FeOOH, and Fig. 3(b) is a TEM (Transmission electron Microscopy) image of β-FeOOH.

[44] Fig. 4(a) is a SEM image of silica coated β-FeOOH according to the method of the present invention, and Fig. 4(b) is a TEM image thereof.

[45] Fig. 5(a) is a SEM image of the obtained nanocapsules after heat treatment was administered to the silica coated β-FeOOH, and Fig. 5(b) and Fig. 5(c) is a TEM image thereof.

[46] Fig. 6(a) and Fig. 6(b) are TEM images of the iron oxide hollow nanocapsules according to the method of the present invention, and Fig.6(c) and Fig.6(d) are high resolution TEM images of the prepared hematite iron oxide hollow nanocapsules. The inset at the upper-right corner of Fig. 6(a) is an image of the hematite iron oxide nanocapsules dispersed in an aqueous solution.

[47] Fig. 7 is X-ray diffraction spectra of (a) β-FeOOH and (b) hematite nanocapsules prepared by the method of the present invention.

[48] Fig. 8(a) is a TEM image of silica coated iron oxide hollow nanocapsules after reduction with hydrogen, and Fig. 8 (a) is a TEM image after removal of silica from said iron oxide hollow nanocapsule, and Fig. 8(c) and Fig. 8(d) are high resolution TEM images of magnetite iron oxide hollow nanocapsules. The inset on Fig. 8(d) is an image of said magnetite iron oxide nanocapsules dispersed in aqueous solution.

[49] Fig. 9 is an X-ray diffraction spectra of the magnetite iron oxide hollow nanocapsules prepared by the method of the present invention.

[50] Fig. 10 is a SEM imag (a) and TEM image (b) of obtained β-FeOOH after undergoing heat treatment without silica coating.

[51] Fig. 11 shows images of the effects of magnetic attraction on hematite (left) and magnetite (right) iron oxide nanocapsules prepared by the method of the present invention.

[52] Fig. 12 shows N2 adsorption isotherms of (a) bulky state, (b) β-FeOOH, (c) hematite hollow nanocapsules, and (d) magnetite hollow nanocapsules.

[53] Fig. 13 shows the pore size distributions calculated from nitrogen absorption experiments of (a) hematite hollow nanocapsules and (b) magnetite hollow nanocapsules. Best Mode for Carrying Out the Invention

[54] Hereinafter, in reference to the accompanying figures, the preferred examples of the present invention will be explained in full detail. The following experiments are provided to fully convey the present invention to a person skilled in the art. Accordingly, the present invention is not to be limited to the following examples, and may be embodied in other forms as well. In addition, the lengths of the layers and thicknesses etc., shown in the figures, may be exaggerated for the sake of convenience. Throughout the whole specification, the same numerals refer to the same constituents.

[55] With reference to Fig. 1, the conventional process for preparing the tubular iron oxide nanoparticle is illustrated, wherein a MgO nanorod is used as a template, and after a metal oxide layer is shaped around the exterior of the molding material, the MgO is etched to prepare the tubular iron oxide nanoparticle.

[56] Fig. 2. shows the preparation process of the iron oxide hollow nanocapsules as one example of the present invention. With reference to Fig. 2, the β-FeOOH prepared by the method of the present invention is used as the metal oxide oxyhydroxide. The β- FeOOH used in the present invention is uniquely characterized is that said β-FeOOH is in a spindle form. The silica coating layer is formed on the spindle β-FeOOH, and after administering heat treatment, as space is formed inside, hematite layer is formed within the inner wall of the silica coating layer. When the silica is removed, a hematite iron oxide hollow nanocapsule is produced. In addition, when heat treatment, which reduces the hematite under hydrogen atmosphere, is carried out before the removal of the silica, the hematite converts to magnetite and thus, magnetite iron oxide hollow nanocapsule is obtained upon removing the silica.

[57] Fig. 3 shows SEM and TEM pictures of the β-FeOOH in the examples of the present invention, which allow confirmation of the uniform shape and size of the prepared β- FeOOH.

[58] Fig. 4 shows SEM and TEM pictures after silica coating layer is formed around said β-FeOOH, which allow confirmation of the uniform formation of the silica coating layer.

[59] Fig. 5 shows SEM and TEM pictures after heat treatment of silica coating layer formed β-FeOOH, and Fig. 6 shows TEM pictures after removal of said silica coating layer which can confirm that the lattice spacing of the crystalline hematite iron oxide is 0.21nm, and that hollow crystalline metal oxide nanocapsules are produced. The prepared spindle-shaped iron oxide hollow nanocapsule with a diameter of IOnm to 20nm and a length of 50nm to lOOnm, is characterized in that the thickness of the shell of said nanocapsule is 5nm to 15nm. The inset at the upper-right corner of Fig. 6(a) is an image which shows that there is almost no precipitation of the iron oxide hollow nanocapsules after dispersion in water for 2 months afer ultrasonic treatment of the hematite iron oxide hollow nanoparticles.

[60] Fig. 7 (a) is the x-ray diffraction spectra of β-FeOOH prepared by hydrolysis of

FeCl₃solution in the example of the present invention, which is used to confirm whether they were identical to known results in the art(JCPDS Card NO. 75-2594), and Fig. 7(b) is the X-ray diffraction spectra of the hematite nanocapsules of the present invention which confirms rhombohedral iron oxide (a = 5.039, c = 13.772, JCPDS Card No. 33-0664), and as are were no other peaks signifying impurities, it is known that pure rhombohedral iron oxide was made.

[61] Fig. 8 (a) is a Transmission Electron Microscope image of silica coated iron oxide hollow nanocapsules after reduction with hydrogen, and Fig 8(b) is a Transmission Electron Microscope image taken after said silica has been removed, and Fig.8(c) and Fig.8(d) are high resolution transmission electron microscope images of magnetite iron oxide hollow nanocapsules, and the inset at the upper-right corner of Fig. 8(d) shows an image of magnetite iron oxide nanocapsules dispersed in an aqueous system. Fig. 9 is the X-ray diffraction spectra of the magnetite iron oxide hollow nanocapsules prepared by the method of the present invention. With reference to Fig. 8 and Fig. 9, it can be seen that the magnetite(Fe₃O₄) with crystal lattice intervals of 0.22nm is formed, and the results of the dispersability experiment with magnetite hollow nanocapsules yielded almost no precipitation compared to the same experiment carried out with hematite hollow nanocapsules, which indicates superior dispersability in aqueous systems.

[62] Fig. 10 shows a Scanning Electron Microscope image of a sample of β-FeOOH after undergoing heat treatment without silica coating (a), and a Transmission Electron Microscope image(b). The images show that because β-FeOOH is normally unstable, heat treatment without undergoing the silica coating process results in the β-FeOOH adhering together and forming into a bulky state, and thus is not able to produce nanocapsules with uniform size and shape.

[63] Fig. 11 shows images of the effects of magnetic attraction on hematite (left) and magnetite(right) iron oxide nanocapsules prepared by the method of the present invention, which indicates ferromagnetism of magnetite iron oxide hollow nanocapsules.

[64] Fig. 12 shows N₂adsorption isotherms of (a) bulky state, (b) β-FeOOH, (c) hematite hollow nanocapsules, and (d) magnetite hollow nanocapsules, and Fig. 13 shows the pore size distributions calculated from nitrogen absorption experiments of hematite hollow nanocapsules(a) and magnetite hollow nanocapsules(b). With reference to Fig. 12 and Fig. 13, the surface area of the hematite hollow nanocapsules and magnetite hollow nanocapsules prepared by the method of the present invention are lόSitfg ¹ and 17 Im^ ¹ respectively, and gross pore volumes are 0.40cm³g ¹ and O^lcrrPg ¹ respectively, and the pore size calculated from the adsorption curves are both 15nm.

[65] Namely, the iron oxide hollow nanocapsules according to the present invention have wide applicability in the fields of catalysts, lithium ion batteries, gas sensors, etc. due to their large surface area and pore volume, and the size and shape of said iron oxide hollow nanocapsules allow for suitable applicability in the biomedical field in applications such as production of extended release formulation of physiologically active materials since said iron oxide nanocapsules have good water-dispersability and can carry physiologically active materials therewithin. As a drug delivery vehicle, the iron oxide hollow nanocapsules have low toxicity, are inexpensive, and can be monitored using their magnetic properties.

[66] Hereinafter, the present invention will be described in more detail through the examples, however examples are given only for illustration of the present invention and are not to limit the scope of the patent claims of the present invention.

[67]

[68] [Example 1]

[69] Preparation of β-FeOOH

[70] 1Og of FeCl₃-OH₂O was dissolved uniformly in distilled water and then stirred for 12 hours at 8O⁰C. After 12 hours, stirring was ceased and the resulting solution was centrifuged to obtain the spindle form of β-FeOOH.

[71]

[72] Preparation of hematite hollow nanocapsules

[73] 300ml of ammonium hydroxide (30 wt.%) was added to a mixed solution of 5L of ethanol and 500ml of distilled water. While being stirred, the β-FeOOH prepared by said method was added, and after 10 minutes, 7ml of tetraethoxysilane was added, and after 10 more minutes of stirring, the β-FeOOH was coated with silica. The resulting material was then centrifuged and the silica coated β-FeOOH was obtained.

[74] The obtained silica coated β-FeOOH was heated up 500⁰C at a rate of 1.5°C/min and maintained at that temperature for 5 hours. After heat treatment, the obtained nano- structure materials were added to 0. IM NaOH and ultrasonic wave treatment was administered for 2 hours to dissolve the silica in order to produce the hematite hollow nanocapsules. The obtained nanomaterials were repeatedly dispersed in distilled water and underwent centrifugation until pH was 7.

[75] With reference to Fig. 6 and Fig. 7, the prepared iron oxide hollow nanocapsules are crystalline hematite with crystal lattice spacing of 0.21nm and a spindle shape with a diameter of IOnm to 20 nm, length of 50nm to 100 nm and shell thickness of 9nm to 1 lnm. The inset in the upper-right corner of Fig. 6(a) is an image which shows that there is almost no precipitation of the metal oxide hollow nanocapsules after 2 months from dispersion in water by way of ultrasonic treatment of the hematite iron oxide hollow nanoparticles.

[76]

[77] [Example 2]

[78] Preparation of magnetite hollow nanoparticles

[79] The nanostructure particles obtained after heat treatment in Experiment 1 were heated for 10 minutes at 500⁰C while a flowing a hydrogen gas flux of lOOsccm whereupon the hematite was converted to magnetite. The obtained nanostructure particles were placed in 0.1 NaOH and centrifuged for 2 hours to dissolve the silica. The obtained nanomaterials were repeatedly dispersed in distilled water and underwent centrifugation until pH was 7.

[80] With reference to Fig. 8 and Fig. 9, the formation of magnetite (Fe₃O₄) with crystal lattice spacing of 0.22nm could be determined, and the results of the dispersability experiment with the magnetite hollow nanocapsules yielded almost no precipitation compared to the same experiment carried out with hematite hollow nanocapsules, which indicates superior dispersability in aqueous systems. In addition, with reference to Fig. 10, when holding a magnet against the side of a container containing magnetite hollow nanocapsules, unlike hematite, the magnetite hollow nanocapsules gathered at the area of the magnet which confirmed the ferromagnetic properties.

[81]

[82] [Comparative Example 1]

[83] Excluding the silica layer coating step of β-FeOOH, iron oxide was prepared by the same process described in Example 1. With reference to Fig. 9, the iron oxide nanoparticles did not form nanostructures, and the β-FeOOH became coagulated with each other which resulted in a bulky formation

[84]

[85] [Examination Example 1]

[86] For the measurements of the specific surface area, pore volume, etc. regarding the materials of Comparative Example l(a), β-FeOOH (b), Experiment l(c), and Experiment 2 (d), Micromeritics ASAP 2000 gas absorption spectrometer was used and a nitrogen adsorption test was carried out which results appear in Fig. 12 and Fig. 13.

[87] Fig. 12 shows the N₂adsorption isotherms, and Fig. 13 shows the pore size distribution calculated from N₂ adsorption test of hematite hollow nanocapsules (a) and magnetite hollow nanocapsules(b). With reference to Fig. 12 and Fig. 13, the surface areas (Brunauer-Emmett-Teller, BET) of the bulky nanocapsules (Comparative Example 1), β-FeOOH, hematite nanocapsules (Example 1), and magnetite nanocapsules (Example 2) were 16.6, 82.3, 165, and 17 Im^ ¹ respectively. Further, gross pore volumes were 0.13, 0.30, 0.40, and O.tMlcitt'g^"1 respectively. Further, the calculated results of pore sizes of hematite nanocapsules (Example 1) and magnetite nanocapsules (Expample 2) from the absorption curve came out to approximately 15nm.

[88]

[89] [Example 3]

[90] Carrying Physiologically Active Materials in Hematite and Magnetite Hollow Nano- capsules

[91] In regards to the iron oxide nanoparticles of Example 1 and Example 2, a drug carrying experiment was carried out using the anti-cancer drug, Doxorubicin.

[92] 2.4mg of Doxorubicin was dissolved in 6mL of water and after dividing in to 1.5mL increments, the Doxorubicin solution (total used amount of Doxorubicin used separately was 0.6mg) was prepared and 0.5mL(1.15 mg Fe used) of iron oxide nanocapsule solution was added to said Doxorubicin solution and then stirred for 24 hours in a darkroom. After 1 hour of centrifugation, the remaining Doxorubicin was measured using UV absorption spectra.

[93] The amount carried in the hematite nanocapsules prepared in Example 1 was

0.178g/g and the amount carried in the magnetite nanocapsultes prepared in Example 2 was 0.289g/g.

Claims

[I] A method for preparing metal oxide hollow nanocapsules, which comprises : a) dispersing metal oxyhydroxide particles in a water and alcohol mixture solution to prepare a metal oxyhydroxide dispersion solution; b) adding a silica precursor agent into the metal and alcohol mixture solution for sol-gel reaction to form the silica coating layer around the metal oxide particle; c) administering heat treatment to make the silica coating layered metal oxide hollow nanocapsules; and d) removing said silica coating layer.

[2] The method according to Claim 1, wherein the metal oxyhydroxide is one selected from the group consisting of β-FeOOH (akaganeite), γ- AlOOH

(boehmite), CoOOH (heterogenite), α-CrOOH (chromia aerogel), InOOH

(indium oxyhydroxide), MnOOH (manganite), NiOOH (nickel oxyhydroxide) and WOOH (tungsten oxyhydroxide). [3] The method according to Claim 1 oxyhydroxide according to claim 2, wherein the metal oxyhydroxide is β-FeOOH. [4] The method according to Claim 3, wherein the β-FeOOH is in the form of a spindle. [5] The method according to Claim 4, wherein β-FeOOH is prepared by dissolving iron salt followed by heating and stirring. [6] The method according to Claim 1, wherein said silica precursor is at least one selected from the group consisting of TEOS (tetraethyl orthosilicate), TMOS

(tetramethyl orthosilicate) and TBOS (tetrabutyl orthosilicate). [7] The method according to Claim 6, wherein the thickness of the silica coating layer is between 2nm and 200nm. [8] The method according to Claim 6, wherein a catalyst used in step b) is selected from the group consisting of ammonium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide. [9] The method according to Claim 1, wherein step d) is carried out by using inorganic base selected from NaOH, KOH and aqueous HF solution. [10] The method according to Claim 1, wherein a temperature of the heat treatment in step c) is maintained between 400⁰C and 1600⁰C.

[I I] The method according to Claim 10, wherein the heat treatment in step c) is carried out by adding a reductant selected from hydrogen gas or NaBH₄.

[12] A metal oxide hollow nanocapsule prepared by the method of any Claim 1 through 11. [13] An iron oxide hollow nanocapsule which is made of hematite (β-Fe₂O₃ ) or magnetite (Fe₃O₄). [14] Said iron oxide hollow nanocapsules according to Claim 13, wherein diameters of the iron oxide hollow nanocapsules are between 10 and 20nm, and length is between 50 and lOOnm in spindle form. [15] The iron oxide hollow nanocapsule of Claim 13 or 14, wherein the hollow area of the iron oxide hollow nanocapsule carries a physiologically active material.