Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex

Anna Maria Piras,1 Angela Fabiano,1 Federica Chiellini,2 Ylenia Zambito1 1Department of Pharmacy, University of Pisa, Pisa, Italy; 2BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Pisa, Italy Purpose: The present study aimed to compare a...

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Autores principales: Piras AM, Fabiano A, Chiellini F, Zambito Y
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Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:fc0b436f5990499badb749b6de2371472021-12-02T06:07:57ZMethyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex1178-2013https://doaj.org/article/fc0b436f5990499badb749b6de2371472018-04-01T00:00:00Zhttps://www.dovepress.com/methyl-beta-cyclodextrin-quaternary-ammonium-chitosan-conjugate-nanopa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Anna Maria Piras,1 Angela Fabiano,1 Federica Chiellini,2 Ylenia Zambito1 1Department of Pharmacy, University of Pisa, Pisa, Italy; 2BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Pisa, Italy Purpose: The present study aimed to compare a novel cyclodextrin–polymer–drug complex in solution with a dispersed supramolecular nanosize system, made of the same complex, for ability to carry dexamethasone (DEX) across excised rat intestine. Results: Methyl-β-cyclodextrin-quaternary ammonium chitosan conjugate (QA-Ch-MCD) was obtained by covalent grafting through a 10-atom spacer. The conjugate was characterized by 1H-NMR, resulting in 24.4% w/w of MCD content. Phase solubility profile analysis of the QA-Ch-MCD/DEX complex yielded an association constant of 14037 M-1, vs 4428 M-1 for the plain MCD/DEX complex. Nanoparticle (NP) dispersions resulted from ionotropic gelation of the QA-Ch-MCD/DEX complex by sodium tripolyphosphate, leading to 9.9%±1.4% drug loading efficiency. The mean diameter and zeta potential for NP were 299±32 nm (polydispersity index [PI] 0.049) and 11.5±1.1 mV, respectively. Those for QA-Ch-MCD/DEX were 2.7±0.4 nm (PI 0.048) and 6.7±0.6 mV. QA-Ch-MCD/DEX solutions and corresponding NP dispersions were compared in vitro for water-assisted transport through mucus, DEX permeation through excised rat intestine, and ex vivo mucoadhesivity. The complex showed higher mucoadhesion and lower transport rate through mucus; also, it provided faster drug permeation across excised rat intestine. Conclusion: Carrier adhesion to mucus surface has played a most important role in favoring transepithelial permeation. Then, within the concerns of the present study, the use of NP seems not to provide any determinant advantage over using the simpler macromolecular complex. Keywords: chitosan derivatives, cyclodextrin chitosan conjugates, mucoadhesive polymers, mucoadhesive nanoparticles, dexamethasone cyclodextrin complexPiras AMFabiano AChiellini FZambito YDove Medical Pressarticlechitosan derivativescyclodextrin chitosan conjugatesmucoadhesive polymersmucoadhesive nanoparticlesdexamethasone cyclodextrin complexMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2531-2541 (2018)
institution DOAJ
collection DOAJ
language EN
topic chitosan derivatives
cyclodextrin chitosan conjugates
mucoadhesive polymers
mucoadhesive nanoparticles
dexamethasone cyclodextrin complex
Medicine (General)
R5-920
spellingShingle chitosan derivatives
cyclodextrin chitosan conjugates
mucoadhesive polymers
mucoadhesive nanoparticles
dexamethasone cyclodextrin complex
Medicine (General)
R5-920
Piras AM
Fabiano A
Chiellini F
Zambito Y
Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex
description Anna Maria Piras,1 Angela Fabiano,1 Federica Chiellini,2 Ylenia Zambito1 1Department of Pharmacy, University of Pisa, Pisa, Italy; 2BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Pisa, Italy Purpose: The present study aimed to compare a novel cyclodextrin–polymer–drug complex in solution with a dispersed supramolecular nanosize system, made of the same complex, for ability to carry dexamethasone (DEX) across excised rat intestine. Results: Methyl-β-cyclodextrin-quaternary ammonium chitosan conjugate (QA-Ch-MCD) was obtained by covalent grafting through a 10-atom spacer. The conjugate was characterized by 1H-NMR, resulting in 24.4% w/w of MCD content. Phase solubility profile analysis of the QA-Ch-MCD/DEX complex yielded an association constant of 14037 M-1, vs 4428 M-1 for the plain MCD/DEX complex. Nanoparticle (NP) dispersions resulted from ionotropic gelation of the QA-Ch-MCD/DEX complex by sodium tripolyphosphate, leading to 9.9%±1.4% drug loading efficiency. The mean diameter and zeta potential for NP were 299±32 nm (polydispersity index [PI] 0.049) and 11.5±1.1 mV, respectively. Those for QA-Ch-MCD/DEX were 2.7±0.4 nm (PI 0.048) and 6.7±0.6 mV. QA-Ch-MCD/DEX solutions and corresponding NP dispersions were compared in vitro for water-assisted transport through mucus, DEX permeation through excised rat intestine, and ex vivo mucoadhesivity. The complex showed higher mucoadhesion and lower transport rate through mucus; also, it provided faster drug permeation across excised rat intestine. Conclusion: Carrier adhesion to mucus surface has played a most important role in favoring transepithelial permeation. Then, within the concerns of the present study, the use of NP seems not to provide any determinant advantage over using the simpler macromolecular complex. Keywords: chitosan derivatives, cyclodextrin chitosan conjugates, mucoadhesive polymers, mucoadhesive nanoparticles, dexamethasone cyclodextrin complex
format article
author Piras AM
Fabiano A
Chiellini F
Zambito Y
author_facet Piras AM
Fabiano A
Chiellini F
Zambito Y
author_sort Piras AM
title Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex
title_short Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex
title_full Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex
title_fullStr Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex
title_full_unstemmed Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex
title_sort methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/fc0b436f5990499badb749b6de237147
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AT fabianoa methylbetacyclodextrinquaternaryammoniumchitosanconjugatenanoparticlesvsmacromolecularsolublecomplex
AT chiellinif methylbetacyclodextrinquaternaryammoniumchitosanconjugatenanoparticlesvsmacromolecularsolublecomplex
AT zambitoy methylbetacyclodextrinquaternaryammoniumchitosanconjugatenanoparticlesvsmacromolecularsolublecomplex
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