Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images.

Author(s) de Azevedo, Mde Burgos; Melo, V.Hs; Soares, C.Rj; Gamarra, L.F.; Barros, C.Hn; Tasic, L.
Journal Int J Nanomedicine
Date Published 2019
Abstract

Introduction: Biodegradable polymers that contain radioactive isotopes such as Holmium 166 have potential applications as beta particle emitters in tumor tissues. Also, Ho(III) is paramagnetic, which makes it suitable as a contrast agent for magnetic resonance (MR) images.

Methods: Holmium acetylacetonate (Ho(acac)) loaded poly(3-hydroxy-butyrate-co-3-hydroxy-valerate) microspheres, with 5% or 8% of 3-hydroxy-valerate (HV), were prepared by emulsification/evaporation process within 20-53 μm size. Microspheres characterization was done using scanning electron microscopy, energy-dispersive X-ray, and infrared spectroscopies. The release of holmium(III) in sodium phosphate buffer (pH 7.4) was followed for 9 days with inductively coupled plasma. Finally, T and T* magnetic resonance images (MRI) were acquired and compared with the MRI of the inclusion complex of holmium acetylacetonate in some β-cyclodextrins.

Results: Holmium acetylacetonate loading, evaluated by thermogravimetry, was up to 20 times higher for copolymer with 5% of HV.It was shown that microspheres loaded with Ho(acac) exhibited an accumulation of Ho(III) on their surfaces but were stable over time, as no expressive release of holmium(III) was detected in 9-day exposition to sodium phosphate buffer. Holmium acetylacetonate in both microspheres or inclusion complexes was very efficient in obtaining T and T* weighted images in magnetic resonance, thus, might be used as contrast agents.

Conclusion: This is the first description of the use of inclusion complexes of holmium acetylacetonate in biodegradable polymers as contrast agents. New investigations are underway to evaluate the resistance of PHB-HV polymer microparticles to nuclear activation to assess their potential for use as radiopharmaceuticals for the treatment of liver cancer.

DOI 10.2147/IJN.S191274
Keywords Calibration; Contrast Media; Holmium; Humans; Hydroxybutyrates; Magnetic Resonance Imaging; Microspheres; Pentanones; Polyesters; Radioisotopes; Spectrometry, X-Ray Emission; Thermogravimetry; X-Ray Diffraction
ISSN 1178-2013
Citation de Azevedo Md, Melo VH, Soares CR, Gamarra LF, Barros CH, Tasic L. Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images. Int J Nanomedicine. 2019;14:6869-6889.

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