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Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy
Kuok,Kit Ieng1; In Ng,Phoebe Choi1; Ji,Xia2; Wang,Chunming1; Yew,Wing Wai3; Chan,Denise P.C.3; Zheng,Jun2; Lee,Simon M.Y.1; Wang,Ruibing1
2018-09-01
Source PublicationFood and Chemical Toxicology
ISSN0278-6915
Volume119Pages:425-429
Abstract

Bedaquiline (BDQ) is a newly approved anti-tuberculosis drug in treating multidrug-resistant tuberculosis. However, it has very poor aqueous solubility and several case reports have proposed that BDQ has potential risk of cardiotoxicity to patients. In this present study, we have explored into employing host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and BDQ aiming to improve the solubility and reduce the inherent cardiotoxicity of BDQ. HPLC-UV test on the solubility of BDQ in the absence and in the presence of increasing concentrations of CB[7] suggested a host-dependent guest-solubility enhancements. Cardiovascular studies using an in vivo zebrafish model demonstrated that the cardiotoxicity of BDQ was indeed alleviated upon its complexations by the synthetic receptor. Furthermore, our in vitro antibacterial studies suggested that CB[7] formulated BDQ preserved its antimycobacterial efficacy against Mycobacterium smegmatis. Therefore, CB[7] may become a suitable pharmaceutical excipient in formulating BDQ for improving its physiochemical properties (such as solubility), and for alleviating its side effects (such as cardiotoxicity), while the antimycobacterial efficacy of BDQ may be well maintained.

KeywordAntimycobacterial Bedaquiline Cardiotoxicity Cucurbit[7]Uril Supramolecular Formulation
DOI10.1016/j.fct.2017.12.022
URLView the original
Indexed BySCIE ; CPCI-S
WOS Research AreaFood Science & Technology ; Toxicology
WOS SubjectFood Science & Technology ; Toxicology
WOS IDWOS:000443664200051
Scopus ID2-s2.0-85038954732
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionDEPARTMENT OF PHARMACEUTICAL SCIENCES
Institute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Corresponding AuthorWang,Ruibing
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Taipa,Macao
2.Faculty of Health Sciences,University of Macau,Taipa,Macao
3.Stanley Ho Centre for Emerging Infectious Diseases,The Chinese University of Hong Kong,Hong Kong
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Kuok,Kit Ieng,In Ng,Phoebe Choi,Ji,Xia,et al. Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy[J]. Food and Chemical Toxicology,2018,119:425-429.
APA Kuok,Kit Ieng,In Ng,Phoebe Choi,Ji,Xia,Wang,Chunming,Yew,Wing Wai,Chan,Denise P.C.,Zheng,Jun,Lee,Simon M.Y.,&Wang,Ruibing.(2018).Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy.Food and Chemical Toxicology,119,425-429.
MLA Kuok,Kit Ieng,et al."Supramolecular strategy for reducing the cardiotoxicity of bedaquiline without compromising its antimycobacterial efficacy".Food and Chemical Toxicology 119(2018):425-429.
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