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Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy

The somatostatin analog octreotide (OCT) displays important neuroprotective and anti-angiogenic properties that could make it an interesting candidate to treat diabetic retinopathy (DR). Unfortunately, systemic drug administration is hindered by severe side effects, therefore topical administration...

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Autores principales: Amato, Rosario, Giannaccini, Martina, Dal Monte, Massimo, Cammalleri, Maurizio, Pini, Alessandro, Raffa, Vittoria, Lulli, Matteo, Casini, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051943/
https://www.ncbi.nlm.nih.gov/pubmed/32158755
http://dx.doi.org/10.3389/fbioe.2020.00144
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author Amato, Rosario
Giannaccini, Martina
Dal Monte, Massimo
Cammalleri, Maurizio
Pini, Alessandro
Raffa, Vittoria
Lulli, Matteo
Casini, Giovanni
author_facet Amato, Rosario
Giannaccini, Martina
Dal Monte, Massimo
Cammalleri, Maurizio
Pini, Alessandro
Raffa, Vittoria
Lulli, Matteo
Casini, Giovanni
author_sort Amato, Rosario
collection PubMed
description The somatostatin analog octreotide (OCT) displays important neuroprotective and anti-angiogenic properties that could make it an interesting candidate to treat diabetic retinopathy (DR). Unfortunately, systemic drug administration is hindered by severe side effects, therefore topical administration routes are preferable. However, drug delivery through eye drops may be difficult due to ocular barriers and, in the long term, could induce ocular damage. On the other hand, intraocular injections must be repeated to maintain drug concentration, and this may cause severe damage to the eye. To decrease injection frequency, long-term release and reduced biodegradation could be obtained by binding the drug to biodegradable polymeric nanoparticles. In the present study, we made a preparation of OCT bound to magnetic nanoparticles (MNP-OCT) and tested its possible use as an OCT delivery system to treat retinal pathologies such as DR. In particular, in vitro, ex vivo, and in vivo experimental models of the mammalian retina were used to investigate the possible toxicity of MNPs, possible effects of the binding to MNPs on OCT bioactivity, and the localization of MNP-OCT in the retina after intraocular injection. The results showed that, both in human retinal endothelial cells (HRECs) and in mouse retinal explants, MNPs were not toxic and the binding with MNPs did not influence OCT antiangiogenic or antiapoptotic activity. Rather, effects of MNP-OCT were observed at concentrations up to 100-fold (in HRECs) or 10-fold (in mouse retinal explants) lower compared to OCT, indicating that OCT bioactivity was enhanced in MNP-OCT. MNP-OCT in mouse retinas in vivo after intraocular delivery were initially localized mainly to the outer retina, at the level of the retinal pigment epithelium, while after 5 days they were observed throughout the retinal thickness. These observations demonstrate that MNP-OCT may be used as an OCT intraocular delivery system that may ensure OCT localization to the retina and enhanced OCT bioactivity. Further studies will be necessary to determine the OCT release rate in the retina and the persistence of drug effects in the long period.
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spelling pubmed-70519432020-03-10 Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy Amato, Rosario Giannaccini, Martina Dal Monte, Massimo Cammalleri, Maurizio Pini, Alessandro Raffa, Vittoria Lulli, Matteo Casini, Giovanni Front Bioeng Biotechnol Bioengineering and Biotechnology The somatostatin analog octreotide (OCT) displays important neuroprotective and anti-angiogenic properties that could make it an interesting candidate to treat diabetic retinopathy (DR). Unfortunately, systemic drug administration is hindered by severe side effects, therefore topical administration routes are preferable. However, drug delivery through eye drops may be difficult due to ocular barriers and, in the long term, could induce ocular damage. On the other hand, intraocular injections must be repeated to maintain drug concentration, and this may cause severe damage to the eye. To decrease injection frequency, long-term release and reduced biodegradation could be obtained by binding the drug to biodegradable polymeric nanoparticles. In the present study, we made a preparation of OCT bound to magnetic nanoparticles (MNP-OCT) and tested its possible use as an OCT delivery system to treat retinal pathologies such as DR. In particular, in vitro, ex vivo, and in vivo experimental models of the mammalian retina were used to investigate the possible toxicity of MNPs, possible effects of the binding to MNPs on OCT bioactivity, and the localization of MNP-OCT in the retina after intraocular injection. The results showed that, both in human retinal endothelial cells (HRECs) and in mouse retinal explants, MNPs were not toxic and the binding with MNPs did not influence OCT antiangiogenic or antiapoptotic activity. Rather, effects of MNP-OCT were observed at concentrations up to 100-fold (in HRECs) or 10-fold (in mouse retinal explants) lower compared to OCT, indicating that OCT bioactivity was enhanced in MNP-OCT. MNP-OCT in mouse retinas in vivo after intraocular delivery were initially localized mainly to the outer retina, at the level of the retinal pigment epithelium, while after 5 days they were observed throughout the retinal thickness. These observations demonstrate that MNP-OCT may be used as an OCT intraocular delivery system that may ensure OCT localization to the retina and enhanced OCT bioactivity. Further studies will be necessary to determine the OCT release rate in the retina and the persistence of drug effects in the long period. Frontiers Media S.A. 2020-02-25 /pmc/articles/PMC7051943/ /pubmed/32158755 http://dx.doi.org/10.3389/fbioe.2020.00144 Text en Copyright © 2020 Amato, Giannaccini, Dal Monte, Cammalleri, Pini, Raffa, Lulli and Casini. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Amato, Rosario
Giannaccini, Martina
Dal Monte, Massimo
Cammalleri, Maurizio
Pini, Alessandro
Raffa, Vittoria
Lulli, Matteo
Casini, Giovanni
Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy
title Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy
title_full Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy
title_fullStr Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy
title_full_unstemmed Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy
title_short Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy
title_sort association of the somatostatin analog octreotide with magnetic nanoparticles for intraocular delivery: a possible approach for the treatment of diabetic retinopathy
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051943/
https://www.ncbi.nlm.nih.gov/pubmed/32158755
http://dx.doi.org/10.3389/fbioe.2020.00144
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