Facile preparation of multifunctional superparamagnetic PHBV microspheres containing SPIONs for biomedical applications.

Wei Li,Monika Pischetsrieder,Christoph Alexiou,Jan Zaloga Jan Zaloga,Yaping Ding,Yufang Liu,Aldo R Boccaccini,Christina Janko

doi:10.1038/srep23140

Abstract

The promising potential of magnetic polymer microspheres in various biomedical applications has been frequently reported. However, the surface hydrophilicity of superparamagnetic iron oxide nanoparticles (SPIONs) usually leads to poor or even failed encapsulation of SPIONs in hydrophobic polymer microspheres using the emulsion method. In this study, the stability of SPIONs in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) solution was significantly increased after surface modification with lauric acid. As a result, magnetic PHBV microspheres with high encapsulation efficiencies (71.0–87.4%) were prepared using emulsion-solvent extraction/evaporation method. Magnetic resonance imaging (MRI) showed significant contrast for the magnetic PHBV microspheres. The toxicity of these magnetic PHBV microspheres towards human T-lymphoma suspension cells and adherent colon carcinoma HT-29 cells was investigated using flow cytometry, and they were shown to be non-toxic in a broad concentration range. A model drug, tetracycline hydrochloride, was used to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres. The drug was successfully loaded into the microspheres using lauric acid-coated SPIONs as drug carrier, and was released from the microspheres in a diffusion controlled manner. The developed magnetic PHBV microspheres are promising candidates for biomedical applications such as targeted drug delivery and MRI.

Highlights

The success of these technologies using magnetic microspheres greatly depends on their preparation from biocompatible and biodegradable polymers of either synthetic[2,8,15,16,17] or natural origin[3,12,18]
Unlike poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA), PHBV does not produce acidic degradation products which may be harmful for human tissues, and it degrades into its monomers in vivo which are normal in the blood[27]
The contrast for MMSH was higher than MMSL at a same concentration due to the higher loading efficiency of SPIONsLA in MMSH. These results show that, SPIONsLA are encapsulated in PHBV microspheres, they can still be used for magnetic imaging applications

Summary

Introduction

The success of these technologies using magnetic microspheres greatly depends on their preparation from biocompatible and biodegradable polymers of either synthetic[2,8,15,16,17] or natural origin[3,12,18]. A good stability of iron oxide nanoparticles in hydrophobic polymer solutions is a prerequisite to the successful fabrication and expanding application of magnetic polymer microspheres. Superparamagnetic iron oxide nanoparticles (SPIONs) were surface modified with lauric acid, which belongs to the family of fatty acid. It was hypothesized that lauric acid could enable the SPIONs to be stable in hydrophobic polymer solution, and facilitate the successful preparation of magnetic polymer microspheres with high encapsulation efficiency/loading efficiency using emulsion-solvent extraction/evaporation method. In the first part of this investigation, SPIONs were surface modified with lauric acid, and encapsulated into PHBV microspheres using solid-in-oil-in-water (S/O/W) emulsion-solvent extraction/evaporation method. In the present study, tetracycline hydrochloride (TCH), a widely used antibiotic, was chosen as a model of water-soluble drugs to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres in vitro

Methods

Results

Conclusion