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Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors

There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gast...

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Autores principales: Abdellatif, Ahmed A. H., Ibrahim, Mohamed A., Amin, Mohammed A., Maswadeh, Hamzah, Alwehaibi, Muhammed N., Al-Harbi, Sultan N., Alharbi, Zayed A., Mohammed, Hamdoon A., Mehany, Ahmed B. M., Saleem, Imran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069942/
https://www.ncbi.nlm.nih.gov/pubmed/32170176
http://dx.doi.org/10.1038/s41598-020-61605-y
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author Abdellatif, Ahmed A. H.
Ibrahim, Mohamed A.
Amin, Mohammed A.
Maswadeh, Hamzah
Alwehaibi, Muhammed N.
Al-Harbi, Sultan N.
Alharbi, Zayed A.
Mohammed, Hamdoon A.
Mehany, Ahmed B. M.
Saleem, Imran
author_facet Abdellatif, Ahmed A. H.
Ibrahim, Mohamed A.
Amin, Mohammed A.
Maswadeh, Hamzah
Alwehaibi, Muhammed N.
Al-Harbi, Sultan N.
Alharbi, Zayed A.
Mohammed, Hamdoon A.
Mehany, Ahmed B. M.
Saleem, Imran
author_sort Abdellatif, Ahmed A. H.
collection PubMed
description There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT.
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spelling pubmed-70699422020-03-22 Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors Abdellatif, Ahmed A. H. Ibrahim, Mohamed A. Amin, Mohammed A. Maswadeh, Hamzah Alwehaibi, Muhammed N. Al-Harbi, Sultan N. Alharbi, Zayed A. Mohammed, Hamdoon A. Mehany, Ahmed B. M. Saleem, Imran Sci Rep Article There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT. Nature Publishing Group UK 2020-03-13 /pmc/articles/PMC7069942/ /pubmed/32170176 http://dx.doi.org/10.1038/s41598-020-61605-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Abdellatif, Ahmed A. H.
Ibrahim, Mohamed A.
Amin, Mohammed A.
Maswadeh, Hamzah
Alwehaibi, Muhammed N.
Al-Harbi, Sultan N.
Alharbi, Zayed A.
Mohammed, Hamdoon A.
Mehany, Ahmed B. M.
Saleem, Imran
Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors
title Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors
title_full Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors
title_fullStr Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors
title_full_unstemmed Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors
title_short Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors
title_sort cetuximab conjugated with octreotide and entrapped calcium alginate-beads for targeting somatostatin receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069942/
https://www.ncbi.nlm.nih.gov/pubmed/32170176
http://dx.doi.org/10.1038/s41598-020-61605-y
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