Biocompatible hydroxy double salts as delivery matrices for non-steroidal anti-inflammatory and anti-epileptic drugs

Abdessamad Y.A. Kaassis; Wafa T. Al-Jamal; Margarita Strimaite; Maja Severic; Gareth R. Williams

doi:10.1016/j.clay.2022.106456

Biocompatible hydroxy double salts as delivery matrices for non-steroidal anti-inflammatory and anti-epileptic drugs

Abdessamad Y.A. Kaassis, Wafa T. Al-Jamal, Margarita Strimaite, Maja Severic, Gareth R. Williams^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

We recently reported the synthesis of two novel biocompatible hydroxy double salts (HDS), [Mg₂Zn₃(OH)₈]Cl₂·3.4H₂O (MgZn-Cl) and [Fe_2.4Zn_2.6(OH)₈]Cl₂·2H₂O (FeZn-Cl) (J. Mater. Chem. B 2016, 4, 5789) and showed them to be suitable for the loading and sustained release of naproxen. Here we build on these findings and report the intercalation, storage stability, biocompatibility and drug release properties of MgZn-Cl and FeZn-Cl loaded with diclofenac, ibuprofen, and valproate. All three active pharmaceutical ingredients could be successfully intercalated into both HDS by ion exchange. An increase in interlayer space from ca. 8 Å to 18.5–27 Å was observed after intercalation, consistent with the replacement of the initial chloride ion with the larger drug anions. Confirmation of successful intercalation was provided by IR spectroscopy, elemental microanalysis, and thermogravimetric analysis. ¹H NMR revealed that the structural integrity of the drug ions is not affected by intercalation. Drug release studies were performed in conditions representative of the gastrointestinal tract, and showed that the solubility of the drug ions controls the fate of the HDS in an acidic environment. The valproate intercalates dissolved completely within two hours at pH 1.0, whereas the other drug-loaded HDS freed some of their drug payload in the acidic media and the rest at pH 6.8. The HDS are further found to be biocompatible in an in vitro cell viability test, and to remain stable upon storage for 5 years.

Original language	English
Article number	106456
Journal	Applied Clay Science
Volume	221
Early online date	01 Mar 2022
DOIs	https://doi.org/10.1016/j.clay.2022.106456
Publication status	Published - May 2022

Bibliographical note

Funding Information:
The authors would like to thank Stephen Boyer of London Metropolitan University for elemental microanalysis measurements, and David McCarthy and Prof Abdul Basit (both UCL School of Pharmacy) for SEM images and access to the automated dissolution system respectively. This work was begun while AYAK was a visiting student at the Beijing University of Chemical Technology, as part of the Sino?UK Higher Education Research Partnership for PhD Studies funded by the British Council China and China Scholarship Council. We thus also thank these bodies.

Funding Information:
The authors would like to thank Stephen Boyer of London Metropolitan University for elemental microanalysis measurements, and David McCarthy and Prof Abdul Basit (both UCL School of Pharmacy ) for SEM images and access to the automated dissolution system respectively. This work was begun while AYAK was a visiting student at the Beijing University of Chemical Technology , as part of the Sino–UK Higher Education Research Partnership for PhD Studies funded by the British Council China and China Scholarship Council . We thus also thank these bodies.

Publisher Copyright:
© 2022 Elsevier B.V.

Keywords

Biocompatibility
Drug delivery
Hydroxy double salts
Intercalation
Sustained release

ASJC Scopus subject areas

Geology
Geochemistry and Petrology

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10.1016/j.clay.2022.106456Licence: Unspecified

Engineering PSMA-targeted exosome-like vesicles to target prostate cancer metastasis
Author: Severic, M., Dec 2022
Supervisor: Al-Jamal, W. (Supervisor) & Burrows, J. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cite this

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title = "Biocompatible hydroxy double salts as delivery matrices for non-steroidal anti-inflammatory and anti-epileptic drugs",

abstract = "We recently reported the synthesis of two novel biocompatible hydroxy double salts (HDS), [Mg2Zn3(OH)8]Cl2·3.4H2O (MgZn-Cl) and [Fe2.4Zn2.6(OH)8]Cl2·2H2O (FeZn-Cl) (J. Mater. Chem. B 2016, 4, 5789) and showed them to be suitable for the loading and sustained release of naproxen. Here we build on these findings and report the intercalation, storage stability, biocompatibility and drug release properties of MgZn-Cl and FeZn-Cl loaded with diclofenac, ibuprofen, and valproate. All three active pharmaceutical ingredients could be successfully intercalated into both HDS by ion exchange. An increase in interlayer space from ca. 8 {\AA} to 18.5–27 {\AA} was observed after intercalation, consistent with the replacement of the initial chloride ion with the larger drug anions. Confirmation of successful intercalation was provided by IR spectroscopy, elemental microanalysis, and thermogravimetric analysis. 1H NMR revealed that the structural integrity of the drug ions is not affected by intercalation. Drug release studies were performed in conditions representative of the gastrointestinal tract, and showed that the solubility of the drug ions controls the fate of the HDS in an acidic environment. The valproate intercalates dissolved completely within two hours at pH 1.0, whereas the other drug-loaded HDS freed some of their drug payload in the acidic media and the rest at pH 6.8. The HDS are further found to be biocompatible in an in vitro cell viability test, and to remain stable upon storage for 5 years.",

keywords = "Biocompatibility, Drug delivery, Hydroxy double salts, Intercalation, Sustained release",

author = "Kaassis, {Abdessamad Y.A.} and Al-Jamal, {Wafa T.} and Margarita Strimaite and Maja Severic and Williams, {Gareth R.}",

note = "Funding Information: The authors would like to thank Stephen Boyer of London Metropolitan University for elemental microanalysis measurements, and David McCarthy and Prof Abdul Basit (both UCL School of Pharmacy) for SEM images and access to the automated dissolution system respectively. This work was begun while AYAK was a visiting student at the Beijing University of Chemical Technology, as part of the Sino?UK Higher Education Research Partnership for PhD Studies funded by the British Council China and China Scholarship Council. We thus also thank these bodies. Funding Information: The authors would like to thank Stephen Boyer of London Metropolitan University for elemental microanalysis measurements, and David McCarthy and Prof Abdul Basit (both UCL School of Pharmacy ) for SEM images and access to the automated dissolution system respectively. This work was begun while AYAK was a visiting student at the Beijing University of Chemical Technology , as part of the Sino–UK Higher Education Research Partnership for PhD Studies funded by the British Council China and China Scholarship Council . We thus also thank these bodies. Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

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doi = "10.1016/j.clay.2022.106456",

language = "English",

volume = "221",

journal = "Applied Clay Science",

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TY - JOUR

T1 - Biocompatible hydroxy double salts as delivery matrices for non-steroidal anti-inflammatory and anti-epileptic drugs

AU - Kaassis, Abdessamad Y.A.

AU - Al-Jamal, Wafa T.

AU - Strimaite, Margarita

AU - Severic, Maja

AU - Williams, Gareth R.

N1 - Funding Information: The authors would like to thank Stephen Boyer of London Metropolitan University for elemental microanalysis measurements, and David McCarthy and Prof Abdul Basit (both UCL School of Pharmacy) for SEM images and access to the automated dissolution system respectively. This work was begun while AYAK was a visiting student at the Beijing University of Chemical Technology, as part of the Sino?UK Higher Education Research Partnership for PhD Studies funded by the British Council China and China Scholarship Council. We thus also thank these bodies. Funding Information: The authors would like to thank Stephen Boyer of London Metropolitan University for elemental microanalysis measurements, and David McCarthy and Prof Abdul Basit (both UCL School of Pharmacy ) for SEM images and access to the automated dissolution system respectively. This work was begun while AYAK was a visiting student at the Beijing University of Chemical Technology , as part of the Sino–UK Higher Education Research Partnership for PhD Studies funded by the British Council China and China Scholarship Council . We thus also thank these bodies. Publisher Copyright: © 2022 Elsevier B.V.

PY - 2022/5

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N2 - We recently reported the synthesis of two novel biocompatible hydroxy double salts (HDS), [Mg2Zn3(OH)8]Cl2·3.4H2O (MgZn-Cl) and [Fe2.4Zn2.6(OH)8]Cl2·2H2O (FeZn-Cl) (J. Mater. Chem. B 2016, 4, 5789) and showed them to be suitable for the loading and sustained release of naproxen. Here we build on these findings and report the intercalation, storage stability, biocompatibility and drug release properties of MgZn-Cl and FeZn-Cl loaded with diclofenac, ibuprofen, and valproate. All three active pharmaceutical ingredients could be successfully intercalated into both HDS by ion exchange. An increase in interlayer space from ca. 8 Å to 18.5–27 Å was observed after intercalation, consistent with the replacement of the initial chloride ion with the larger drug anions. Confirmation of successful intercalation was provided by IR spectroscopy, elemental microanalysis, and thermogravimetric analysis. 1H NMR revealed that the structural integrity of the drug ions is not affected by intercalation. Drug release studies were performed in conditions representative of the gastrointestinal tract, and showed that the solubility of the drug ions controls the fate of the HDS in an acidic environment. The valproate intercalates dissolved completely within two hours at pH 1.0, whereas the other drug-loaded HDS freed some of their drug payload in the acidic media and the rest at pH 6.8. The HDS are further found to be biocompatible in an in vitro cell viability test, and to remain stable upon storage for 5 years.

AB - We recently reported the synthesis of two novel biocompatible hydroxy double salts (HDS), [Mg2Zn3(OH)8]Cl2·3.4H2O (MgZn-Cl) and [Fe2.4Zn2.6(OH)8]Cl2·2H2O (FeZn-Cl) (J. Mater. Chem. B 2016, 4, 5789) and showed them to be suitable for the loading and sustained release of naproxen. Here we build on these findings and report the intercalation, storage stability, biocompatibility and drug release properties of MgZn-Cl and FeZn-Cl loaded with diclofenac, ibuprofen, and valproate. All three active pharmaceutical ingredients could be successfully intercalated into both HDS by ion exchange. An increase in interlayer space from ca. 8 Å to 18.5–27 Å was observed after intercalation, consistent with the replacement of the initial chloride ion with the larger drug anions. Confirmation of successful intercalation was provided by IR spectroscopy, elemental microanalysis, and thermogravimetric analysis. 1H NMR revealed that the structural integrity of the drug ions is not affected by intercalation. Drug release studies were performed in conditions representative of the gastrointestinal tract, and showed that the solubility of the drug ions controls the fate of the HDS in an acidic environment. The valproate intercalates dissolved completely within two hours at pH 1.0, whereas the other drug-loaded HDS freed some of their drug payload in the acidic media and the rest at pH 6.8. The HDS are further found to be biocompatible in an in vitro cell viability test, and to remain stable upon storage for 5 years.

KW - Biocompatibility

KW - Drug delivery

KW - Hydroxy double salts

KW - Intercalation

KW - Sustained release

U2 - 10.1016/j.clay.2022.106456

DO - 10.1016/j.clay.2022.106456

M3 - Article

AN - SCOPUS:85126739349

VL - 221

JO - Applied Clay Science

JF - Applied Clay Science

SN - 0169-1317

M1 - 106456

ER -

Biocompatible hydroxy double salts as delivery matrices for non-steroidal anti-inflammatory and anti-epileptic drugs

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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Student theses

Engineering PSMA-targeted exosome-like vesicles to target prostate cancer metastasis

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