Elsevier

Materials Chemistry and Physics

Volume 207, 1 March 2018, Pages 243-252
Materials Chemistry and Physics

Magnetite-based nanobioplatform for site delivering Croton cajucara Benth essential oil

https://doi.org/10.1016/j.matchemphys.2017.12.058Get rights and content

Highlights

  • Double-coated (OA & EO) magnetite nanoparticles were successfully synthesized.

  • Good superparamagnetic features were found for the double-coated nanostructure.

  • The EO release at low T’s makes the nanostructure interesting for site delivering.

  • The studied nanostructure shows potential for combining diagnostic and therapy.

Abstract

Surface coating magnetic nanoparticles can be realized using organic moieties, such as essential oil (EO) extracted from Croton cajucara Benth leaves, a common plant from the Brazilian Amazon region successfully used for infusion in popular medicine. Although, there are reports in the literature indicating the protective and healing actions of the EO on gastric lesions, the inclusion of the magnetic core to control (targeting and retaining) the MNPs in specific sites can improve the performance of the EO molecules for the treatment of gastric disorders. Therefore, in this work, we report on fabrication and characterization of surface-coated magnetite nanoparticles (MNPs), aiming thermal-assisted site delivering EO. Firstly, oleic acid (OA) coated MNPs (sample M1) were fabricated using a thermal decomposition route. Secondly, the OA-coated MNPs were dressed with EO (sample M2). Meanwhile, x-ray diffraction and transmission electron microscopy data confirmed formation of spherically-shaped magnetite core while successful single OA coating and double OA + EO coating of MNPs was confirmed by infrared spectroscopy and thermogravimetric analysis (TGA). TGA results indicated release of the EO at ∼50 °C, whereas the OA is released only above ∼380 °C. Blocking (TB) and irreversible (TIRR) temperatures of samples M1 (TB = 210 K; TIRR = 210 K) and M2 (TB = 35 K; TIRR = 215 K) were assessed from magnetic measurements data analysis. In sample M2, the difference TB-TIRR (180 K) was related to inhomogeneous partial shifting of OA molecules by EO molecules whereas the remarkable reduction of MS with respect to sample M1 was assigned to a dead surface layer dominated by ferrous ions in low-spin state. Moreover, the lower TB value we have found in sample M2 (∼35 K) indicates negligible particle-particle interactions due to the successful double coating (OA plus EO) of the MNPs, in contrast to that obtained in sample M1. In sample M2 weakening of particle-particle interaction warrants superparamagnetic properties which can be used to obtain magnetic resonance image and for guiding the MNPs to targeting sites using gradients of external magnetic field. Therefore, the combination of the improved magnetic properties plus the detachment of EO at ∼50 °C (while keeping stable the OA coating) via magnetohyperthermia makes the double coated system (sample M2) a very promising candidate for site delivering of EO to treat gastrointestinal disorders.

Introduction

In recent years, nanoscience has developed steeply since it was recognized that nanostructured materials show unique and modulated properties, depending for instance on size, shape, and surface coating [1], [2]. Iron oxide nanoparticles (NPs) comprise a wide class of nanomaterials, which are of great interest for biological and medical applications credited to their superior biocompatibility, biodegradation and safe excretion routes while within living systems [3], [4]. Among magnetic NPs magnetite (Fe3O4) has raised huge interest and found many applications in biology and medicine, as for example in cell manipulation and contrast agent for magnetic resonance imaging [5], [6]. Structurally, bulk magnetite shows an inverse spinel structure, in which oxygen atoms form a face centered cubic lattice and iron ions (Fe2+ and Fe3+) occupy tetrahedral and octahedral sites. Within magnetite's crystal structure electron transferring from ferrous to ferric ion has been reported at room temperature, i.e. above the Verwey transition ∼125 K. As far as biological and medical applications are concerned, after synthesizing pristine magnetite nanoparticles (MNPs) surface coating should be the next step to follow in order to incorporate functionality, site specificity, and enhanced biocompatibility. Moreover, surface coating also promotes colloidal stability via electrostatic and/or steric interactions, preventing suspended single units in liquid media to aggregate themselves into larger clusters driven by attractive interactions such as magnetic dipole-dipole and Van der Walls and leading to decreased effective magnetization and deleterious biological response [7].

Surface coating MNPs can be realized using organic moieties, such as fatty acids with long tail, in which case the polar carboxyl group complexes the MNP's surface while the hydrophobic tail provides steric repulsion [8]. Additionally, it is possible to carry out surface coating with multiple layers of surfactants, in which case the inner surface layer can be further dressed with a second and third one, the outer layer being for instance a specific drug [9]. In this way, the first coating layer may offers both stable dispersion for the MNP in a suitable solvent and favorable anchoring environment for the next layer, which are meant to provide special features to the end nanomaterial, such as bioactive characteristics [10]. Moreover, MNPs can be manipulated by applying external magnetic field gradients with the interest of moving and fixing the surface-functionalized MNPs in a specific biological site, where a particular bioactive molecule is engineered to be delivered, thus facilitating the direct and effective interaction between the target site and the bioactive molecule [11]. This approach minimizes risks of biological side effects related to excessive dose level exposition. Besides, in the case of non-interacting superparamagnetic MNPs reversible dispersion while in suspension in liquid media would be quickly achieved as one removes the external magnetic field gradient, thus favoring routes of excretion out from the living host [12].

Indeed, engineering nanomaterials' surface is an essential step for successful biological and medical applications. In this way, several compounds have been tested, such as dextran, chitosan, dimercaptosuccinic acid (DMSA), and polyethylene glycol (PEG) [[13], [14], [15]]. Other compound commonly used to provide colloidal stability is the oleic acid (OA) [16], which can be used as an anchor agent for a second layer with bioactive features. In this regard, a very interesting substance is the essential oil (EO) obtained from the Croton cajucara Benth leaves, a common plant from the Brazilian Amazon region and successfully used for infusion in popular medicine against gastrointestinal and liver disorders, diabetes, and for reducing higher levels of cholesterol [[17], [18], [19]].

Although, the antiulcerogenic activity of the EO has been extensively studied for the treatment of gastric ulcers, the exact mechanism is not clear yet (HIRUMA-LIMA et al., 2002). It is known that the ulcerative process is complex, and there are many factors involved. It is known that the arising of ulcers is a consequence of an imbalance between mucosal gastro protective factors (mucus secretion, bicarbonate production, etc.) and the components that can cause injury (acid secretions, pepsin, etc.) [20]. Himura-Lima et al. [18], reported that the EO extracted from Croton cajucara Benth shows the ability to increase the prostaglandins (PGE2) release from mucus cells of the stomach tissue, which favors the gastro protective effect in the case of lesions due to ulcers. Additionally, an increase in the release of PGE2, inhibit the physiological responses that would be caused by the production of histamines (among them the most important is the gastric acid secretion by the parietal cells) [21].

Besides, previous studies have demonstrated that the linalool-rich EO extracted from Croton cajucara Benth is extremely efficient for treating tegumentary Leishmania amazonensis [19]. Due to the chemical structure of the main component (linalool) of the EO extracted from the Croton cajucara Benth leaves it can be used as a second layer on top of for instance oleic acid (OA) pre-coated MNPs. More advantageously, the EO-coated MNPs can be dispersed in excess of EO carrier to produce a very stable magnetic fluid sample. Finally, magnetite-based core-shell nanostructures can be fabricated using the above-mentioned scheme in order to take advantage of the magnetic properties of the core plus the medicinal properties of the shell. This material platform could be successfully used as a vector in medical applications, such as in association with magnetohyperthermia, as it will be emphasized later on in this report. Additionaly, innovative applications that combine both diagnostic and therapeutic elements in biomedicine (theranostics), can be obtained using MNPs which can be used to deliver a remediation agent to target sites using magnetohyperthermia while the diagnostic capability of monitoring the biodistribution of the particles can be obtained using magnetic resonance images (MRI) [22], [23].

In this study, we report on the synthesis and characterization of spherically shaped MNPs with average diameter of ∼10 nm and very low diameter polydispersity index (around 0.16). More interesting, the employed synthesis route used a single step (one-pot approach) for fabrication of OA-coated MNPs, thus protecting the core phase to be quickly oxidized into ferric oxide phases. Two samples were fabricated and characterized, namely OA-coated MNPs (sample M1) and MNPs coated with a first layer of OA plus a second layer of EO (sample M2). The structural, morphological, optical, thermal and magnetic properties of the core-shell structure before and after the second coating (EO-coating) is herein reported. The magnetic results indicated that the additional coating layer improves the magnetic properties of the double layer coated (OA + EO) MNPs, which are important to control the reversible dispersion while in suspension in a liquid media. We anticipate that sample M2 is a very good candidate for site delivering the outer moiety (EO) for a therapeutic purposes against, for instance, gastrointenstinal ulcers. The detachment of EO moiety can be remotely activated by AC magnetic field using the magnetohyperthermia (MHT) effect due to the low temperature of EO release. Moreover, due to the well know biocompatibility of OA-coated MNPs [24] the material platform provided by sample M2 is ready to be tested using in vitro as well as in vivo assays. Meanwhile, the EO outer covering layer of the MNPs can be used for the therapeutic action, the magnetic core can also be explored for diagnostic purposes via magnetic resonance image.

Section snippets

Nanoparticle fabrication

The synthesis of OA-coated MNPs was carried out using a variation of the protocol reported elsewhere [25]. In short, ferric acetylacetonate (2 mmol), 1,2-hexadecanodiol (10 mmol), benzyl ether (20 mL), oleic acid (6 mmol) and oleylamine (6 mmol) were placed in a three-neck round-bottom flask under argon flow. Thereafter, the system was mixed homogeneously with a magnetic stirrer while increasing the temperature up to 220 °C, meanwhile maintaining the stirring for 2 h. Next, the temperature was

Results and discussion

As reported in the literature [25], [30] thermal decomposition of ferric acetate in presence of benzyl ether and oleic acid provides one-pot synthesis route for fabrication of MNPs surface-coated with OA (sample M1). In this case, OA also provides size control during the synthesis process while dressing the growing MNPs. Moreover, the OA carboxylate group is assumed to attach onto the MNP's surface while the OA hydrocarbon tail faces outwards and provides steric repulsion in non-polar liquid

Conclusions

Monodispersed core magnetite nanoparticles with average diameter ∼10 nm were successfully synthesized and surface-coated with oleic acid (sample M1) and oleic acid plus essential oil (sample M2). Both samples were characterized using a variety of experimental techniques (XRD, TEM, FTIR, TGA, MM), confirming successful single-coating layer (sample M1) and double-coating layer (sample M2). The data assessed from TGA showed a reduction of oleic acid (OA) content in sample M2 (67.5%) while compared

Acknowledgments

Authors want to thank CAPES, CNPq and FAP/DF for financial support. Special thanks to Dr. E. Mendes from Institute of Geoscience of the University of Brasilia for the X-ray diffraction experiments and Dr. M. J. A. Sales from Institute of Chemistry of the University of Brasilia for the TGA measurements.

References (59)

  • J. Mamani et al.

    Synthesis and characterization of magnetite nanoparticles coated with lauric acid

    Mater. Char.

    (2013)
  • V. Patsula et al.

    Size-dependent magnetic properties of iron oxide nanoparticles

    J. Phys. Chem. Solid.

    (2016)
  • I. Martínez-Mera et al.

    Synthesis of magnetite (Fe 3 O 4) nanoparticles without surfactants at room temperature

    Mater. Lett.

    (2007)
  • Q. Lan et al.

    Synthesis of bilayer oleic acid-coated Fe 3 O 4 nanoparticles and their application in pH-responsive Pickering emulsions

    J. Colloid Interface Sci.

    (2007)
  • L. Zhang et al.

    Oleic acid coating on the monodisperse magnetite nanoparticles

    Appl. Surf. Sci.

    (2006)
  • N.V. Jadhav et al.

    Synthesis of oleic acid functionalized Fe 3 O 4 magnetic nanoparticles and studying their interaction with tumor cells for potential hyperthermia applications

    Colloids Surfaces B Biointerfaces

    (2013)
  • D. Li et al.

    An easy fabrication of monodisperse oleic acid-coated Fe 3 O 4 nanoparticles

    Mater. Lett.

    (2010)
  • Y.-S. Li et al.

    Infrared and Raman spectroscopic studies on iron oxide magnetic nano-particles and their surface modifications

    J. Magn. Magn Mater.

    (2012)
  • P. Pradhan et al.

    Cellular interactions of lauric acid and dextran-coated magnetite nanoparticles

    J. Magn. Magn Mater.

    (2007)
  • A. Semkina et al.

    Core–shell–corona doxorubicin-loaded superparamagnetic Fe 3 O 4 nanoparticles for cancer theranostics

    Colloids Surfaces B Biointerfaces

    (2015)
  • P. Pradhan et al.

    Preparation and characterization of manganese ferrite-based magnetic liposomes for hyperthermia treatment of cancer

    J. Magn. Magn Mater.

    (2007)
  • C. Meiorin et al.

    Nanocomposites with superparamagnetic behavior based on a vegetable oil and magnetite nanoparticles

    Eur. Polym. J.

    (2014)
  • F. Ogata et al.

    Pressure-induced high-spin-low-spin transition in transition metal compounds

    J. Magn. Magn Mater.

    (1983)
  • P. Guardia et al.

    Surfactant effects in magnetite nanoparticles of controlled size

    J. Magn. Magn Mater.

    (2007)
  • C. Di Paola et al.

    Geometrical effects on the magnetic properties of nanoparticles

    Nano Lett.

    (2016)
  • K.C. de Souza et al.

    Nanocompósitos magnéticos: potencialidades de aplicações em biomedicina

    Quím. Nova

    (2011)
  • J.P.M. Almeida et al.

    In vivo biodistribution of nanoparticles

    Nanomedicine

    (2011)
  • V. Patsula et al.

    Superparamagnetic Fe3O4 nanoparticles: synthesis by thermal decomposition of iron (III) glucuronate and application in magnetic resonance imaging

    ACS Appl. Mater. Interfaces

    (2016)
  • A.H. Lu et al.

    Magnetic nanoparticles: synthesis, protection, functionalization, and application

    Angew. Chem. Int. Ed.

    (2007)
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