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

Authors de Azevedo MBM, Melo VHS, Soares CRJ, Gamarra LF, Barros CHN, Tasic L

Received 18 October 2018

Accepted for publication 11 March 2019

Published 29 August 2019 Volume 2019:14 Pages 6869—6889

DOI https://doi.org/10.2147/IJN.S191274

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo


Mariangela de Burgos M de Azevedo,1 Vitor HS Melo,1 Carlos RJ Soares,1 Lionel F Gamarra,2 Caio HN Barros,3,4 Ljubica Tasic4

1Centro de Biotecnologia, IPEN/CNEN-SP, São Paulo, Brazil; 2Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 3School of Chemical and Bioprocess Engineering, University College Dublin, Dublin, Ireland; 4Instituto de Química, UNICAMP, SP, Campinas, Brazil

Correspondence: Mariangela de Burgos M de Azevedo
Centro de Biotecnologia, IPEN/Cnen-SP, São Paulo, Brazil, 05508-000
Email mariangela.burgos@cnpq.pq.br

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)3) 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, T2 and T2* 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)3 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 T2 and T2* 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.

Keywords: holmium acetylacetonate, PHB-HV microparticles, microspheres, MRI

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