Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images
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 Tasic41Centro de Biotecnologia, IPEN/CNEN-SP, São Paulo, Brazil; 2Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 3School of Chemical and Bioprocess E...
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Dove Medical Press
2019
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oai:doaj.org-article:7cc97ae6017b4cb3a6b7c8b5db7a08a52021-12-02T04:07:21ZPoly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images1178-2013https://doaj.org/article/7cc97ae6017b4cb3a6b7c8b5db7a08a52019-08-01T00:00:00Zhttps://www.dovepress.com/poly3-hydroxi-butyrate-co-3-hydroxy-valerate-phb-hv-microparticles-loa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mariangela de Burgos M de Azevedo,1 Vitor HS Melo,1 Carlos RJ Soares,1 Lionel F Gamarra,2 Caio HN Barros,3,4 Ljubica Tasic41Centro 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, BrazilCorrespondence: Mariangela de Burgos M de AzevedoCentro de Biotecnologia, IPEN/Cnen-SP, São Paulo, Brazil, 05508-000Email mariangela.burgos@cnpq.pq.brIntroduction: 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, MRIde Azevedo MBMMelo VHSSoares CRJGamarra LFBarros CHNTasic LDove Medical PressarticleHolmium acetylacetonatePHB-HV microparticlesmicrospheresMRIMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6869-6889 (2019) |
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Holmium acetylacetonate PHB-HV microparticles microspheres MRI Medicine (General) R5-920 |
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Holmium acetylacetonate PHB-HV microparticles microspheres MRI Medicine (General) R5-920 de Azevedo MBM Melo VHS Soares CRJ Gamarra LF Barros CHN 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 |
description |
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 Tasic41Centro 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, BrazilCorrespondence: Mariangela de Burgos M de AzevedoCentro de Biotecnologia, IPEN/Cnen-SP, São Paulo, Brazil, 05508-000Email mariangela.burgos@cnpq.pq.brIntroduction: 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 |
format |
article |
author |
de Azevedo MBM Melo VHS Soares CRJ Gamarra LF Barros CHN Tasic L |
author_facet |
de Azevedo MBM Melo VHS Soares CRJ Gamarra LF Barros CHN Tasic L |
author_sort |
de Azevedo MBM |
title |
Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images |
title_short |
Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images |
title_full |
Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images |
title_fullStr |
Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images |
title_full_unstemmed |
Poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (PHB-HV) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images |
title_sort |
poly(3-hydroxi-butyrate-co-3-hydroxy-valerate) (phb-hv) microparticles loaded with holmium acetylacetonate as potential contrast agents for magnetic resonance images |
publisher |
Dove Medical Press |
publishDate |
2019 |
url |
https://doaj.org/article/7cc97ae6017b4cb3a6b7c8b5db7a08a5 |
work_keys_str_mv |
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