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Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Chitosan is a natural polymer revealing an increased potential to be used in different biomedical applications, including drug delivery systems, and tissue engineering. It implies the evaluation of the organism response to the biomaterial implantation. Low-molecular degradation products, the chito-o...

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Autores principales: Roman, Diana Larisa, Roman, Marin, Som, Claudia, Schmutz, Mélanie, Hernandez, Edgar, Wick, Peter, Casalini, Tommaso, Perale, Giuseppe, Ostafe, Vasile, Isvoran, Adriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743017/
https://www.ncbi.nlm.nih.gov/pubmed/31552240
http://dx.doi.org/10.3389/fbioe.2019.00214
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author Roman, Diana Larisa
Roman, Marin
Som, Claudia
Schmutz, Mélanie
Hernandez, Edgar
Wick, Peter
Casalini, Tommaso
Perale, Giuseppe
Ostafe, Vasile
Isvoran, Adriana
author_facet Roman, Diana Larisa
Roman, Marin
Som, Claudia
Schmutz, Mélanie
Hernandez, Edgar
Wick, Peter
Casalini, Tommaso
Perale, Giuseppe
Ostafe, Vasile
Isvoran, Adriana
author_sort Roman, Diana Larisa
collection PubMed
description Chitosan is a natural polymer revealing an increased potential to be used in different biomedical applications, including drug delivery systems, and tissue engineering. It implies the evaluation of the organism response to the biomaterial implantation. Low-molecular degradation products, the chito-oligomers, are resulting mainly from the influence of enzymes, which are found in the organism fluids. Within this study, we have performed the computational assessment of pharmacological profiles and toxicological effects on human health of small chito-oligomers with distinct molecular weights, deacetylation degrees, and acetylation patterns. Our approach is based on the fact that regulatory agencies and researchers in the drug development field rely on the use of modeling to predict biological effects and to guide decision making. To be considered as valid for regulatory purposes, every model that is used for predictions should be associated with a defined toxicological endpoint and has appropriate robustness and predictivity. Within this context, we have used FAF-Drugs4, SwissADME, and PreADMET tools to predict the oral bioavailability of chito-oligomers and SwissADME, PreADMET, and admetSAR2.0 tools to predict their pharmacokinetic profiles. The organs and genomic toxicities have been assessed using admetSAR2.0 and PreADMET tools but specific computational facilities have been also used for predicting different toxicological endpoints: Pred-Skin for skin sensitization, CarcinoPred-EL for carcinogenicity, Pred-hERG for cardiotoxicity, ENDOCRINE DISRUPTOME for endocrine disruption potential and Toxtree for carcinogenicity and mutagenicity. Our computational assessment showed that investigated chito-oligomers reflect promising pharmacological profiles and limited toxicological effects on humans, regardless of molecular weight, deacetylation degree, and acetylation pattern. According to our results, there is a possible inhibition of the organic anion transporting peptides OATP1B1 and/or OATP1B3, a weak potential of cardiotoxicity, a minor probability of affecting the androgen receptor, and phospholipidosis. Consequently, these results may be used to guide or to complement the existing in vitro and in vivo toxicity tests, to optimize biomaterials properties and to contribute to the selection of prototypes for nanocarriers.
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spelling pubmed-67430172019-09-24 Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan Roman, Diana Larisa Roman, Marin Som, Claudia Schmutz, Mélanie Hernandez, Edgar Wick, Peter Casalini, Tommaso Perale, Giuseppe Ostafe, Vasile Isvoran, Adriana Front Bioeng Biotechnol Bioengineering and Biotechnology Chitosan is a natural polymer revealing an increased potential to be used in different biomedical applications, including drug delivery systems, and tissue engineering. It implies the evaluation of the organism response to the biomaterial implantation. Low-molecular degradation products, the chito-oligomers, are resulting mainly from the influence of enzymes, which are found in the organism fluids. Within this study, we have performed the computational assessment of pharmacological profiles and toxicological effects on human health of small chito-oligomers with distinct molecular weights, deacetylation degrees, and acetylation patterns. Our approach is based on the fact that regulatory agencies and researchers in the drug development field rely on the use of modeling to predict biological effects and to guide decision making. To be considered as valid for regulatory purposes, every model that is used for predictions should be associated with a defined toxicological endpoint and has appropriate robustness and predictivity. Within this context, we have used FAF-Drugs4, SwissADME, and PreADMET tools to predict the oral bioavailability of chito-oligomers and SwissADME, PreADMET, and admetSAR2.0 tools to predict their pharmacokinetic profiles. The organs and genomic toxicities have been assessed using admetSAR2.0 and PreADMET tools but specific computational facilities have been also used for predicting different toxicological endpoints: Pred-Skin for skin sensitization, CarcinoPred-EL for carcinogenicity, Pred-hERG for cardiotoxicity, ENDOCRINE DISRUPTOME for endocrine disruption potential and Toxtree for carcinogenicity and mutagenicity. Our computational assessment showed that investigated chito-oligomers reflect promising pharmacological profiles and limited toxicological effects on humans, regardless of molecular weight, deacetylation degree, and acetylation pattern. According to our results, there is a possible inhibition of the organic anion transporting peptides OATP1B1 and/or OATP1B3, a weak potential of cardiotoxicity, a minor probability of affecting the androgen receptor, and phospholipidosis. Consequently, these results may be used to guide or to complement the existing in vitro and in vivo toxicity tests, to optimize biomaterials properties and to contribute to the selection of prototypes for nanocarriers. Frontiers Media S.A. 2019-09-06 /pmc/articles/PMC6743017/ /pubmed/31552240 http://dx.doi.org/10.3389/fbioe.2019.00214 Text en Copyright © 2019 Roman, Roman, Som, Schmutz, Hernandez, Wick, Casalini, Perale, Ostafe and Isvoran. 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
Roman, Diana Larisa
Roman, Marin
Som, Claudia
Schmutz, Mélanie
Hernandez, Edgar
Wick, Peter
Casalini, Tommaso
Perale, Giuseppe
Ostafe, Vasile
Isvoran, Adriana
Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan
title Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan
title_full Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan
title_fullStr Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan
title_full_unstemmed Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan
title_short Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan
title_sort computational assessment of the pharmacological profiles of degradation products of chitosan
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743017/
https://www.ncbi.nlm.nih.gov/pubmed/31552240
http://dx.doi.org/10.3389/fbioe.2019.00214
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