Novel aqueous nano-scaled formulations of oleic acid stabilized hydrophobic superparamagnetic iron oxide nanocrystals

Abstract

Background: Novel aqueous nano-scaled formulations were developed for hydrophobic oleic acid stabilized monodisperse superparamagnetic magnetite nanocrystals.

Methods: In the study, single and mixed lipid amphiphiles based on Cremophor RH-40 (Crem-RH-40), Solutol HS-15 (Sol-HS-15), Phospholipon-100H (PL-100H) and sucrose ester M-1695 (SE-M-1695) were employed at varying concentrations. Isotonicity and physiological pH adjustments were achieved by using 5% w/v mannitol in 10 mM pH 7.4 phosphate buffer. Mannitol also served as lyoprotectant for the freeze drying of selected formulation. The developed formulations were characterized by photon correlation spectroscopy (PCS) and asymmetric flow field flow fractionation methods for their size and size distributions and morphologies were examined by transmission electron microscopy (TEM). Moreover, the potential magnetic resonance imaging (MRI) contrast agent application of a selected formulation was investigated by ¹H-NMR relaxometric measurements.

Results: The results showed that stable formulations of the nanocrystals with hydrodynamic diameters generally below 100 nm were obtained. Among the developed formulations, the one prepared with 0.75% Crem-RH-40, 0.5% PL-100H and 0.25% SE-M-1695 had a mean hydrodynamic diameter of ~64 nm and zeta potential of −20 mV. This formulation exhibited low degree of aggregation, high level of incorporation of magnetite nanocrystals and very good stability profile over a period of 6 months. In addition, it showed transverse and longitudinal relaxivities of 221.8 and 32.1 s⁻¹·mM⁻¹, respectively with r₂/r₁ ratio of 6.9.

Conclusion: This study revealed that mixed lipid-based amphiphiles allow stable aqueous formulations of the normally challenging hydrophobic magnetite nanocrystals with potential in vivo MRI contrast applications.

Keywords::

• Magnetite nanocrystals
• Cremophor
• Solutol
• sucrose ester
• hydrophilization
• asymmetric flow field flow fractionation
• ¹H-NMR relaxometry
• freeze drying
• autoclaving

Acknowledgements

The authors would like to cordially thank Dr. Judith Kuntsche of the Institute of Pharmacy, MLU-HW for the unreserved help with the asymmetric flow field flow fractionation experiments, Dr. Gerd Hause of the Biocenter, MLU-HW for the TEM experiments and Mr. Frank Syrowatka of the Interdisciplinary Center of Materials Science, MLU-HW for the ESEM experiments. Acknowledgement also goes to the German Academic Exchange Service (DAAD) for the financial support provided to A.B.

Declaration of interest

This work was financially supported by the German Academic Exchange Service (DAAD).The authors report no conflicts of interest.