Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity

Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity

Xiaolong Tang,1,2,* Yong Liang,3,* Yongqiang Zhu,1,4,* Chunmei Xie,5 Aixia Yao,1 Li Chen,1 Qinglin Jiang,1 Tingting Liu,1 Xiaoyu Wang,1 Yunyun Qian,1 Jia Wei,1 Wenxuan Ni,1 Jingjing Dai,1 Zhenyou Jiang,6,7,* Wei Hou2,* 1Clinical Laboratory, Huainan First People’s Hospital and First Affili...

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Autores principales: Tang X, Liang Y, Zhu Y, Xie C, Yao A, Chen L, Jiang Q, Liu T, Wang X, Qian Y, Wei J, Ni W, Dai J, Jiang Z, Hou W
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/e655dafc621b4617aced508bf92bf5ab
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spelling oai:doaj.org-article:e655dafc621b4617aced508bf92bf5ab2021-12-02T00:37:16ZAnti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity1178-2013https://doaj.org/article/e655dafc621b4617aced508bf92bf5ab2015-10-01T00:00:00Zhttps://www.dovepress.com/anti-transferrin-receptor-modified-amphotericin-b-loaded-plandashpeg-n-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaolong Tang,1,2,* Yong Liang,3,* Yongqiang Zhu,1,4,* Chunmei Xie,5 Aixia Yao,1 Li Chen,1 Qinglin Jiang,1 Tingting Liu,1 Xiaoyu Wang,1 Yunyun Qian,1 Jia Wei,1 Wenxuan Ni,1 Jingjing Dai,1 Zhenyou Jiang,6,7,* Wei Hou2,* 1Clinical Laboratory, Huainan First People’s Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, 2State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, 3Clinical Laboratory, Huai’an Hospital Affiliated of Xuzhou Medical College, Huaian, 4Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 5School of Biotechnology, Southern Medical University, 6Department of Microbiology and Immunology, School of Medicine, 7Guangdong Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood–brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])–PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection. Keywords: drug delivery, nanocarrier, amphotericin B, blood–brain barrier, transferrin receptorTang XLiang YZhu YXie CYao AChen LJiang QLiu TWang XQian YWei JNi WDai JJiang ZHou WDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6227-6241 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Tang X
Liang Y
Zhu Y
Xie C
Yao A
Chen L
Jiang Q
Liu T
Wang X
Qian Y
Wei J
Ni W
Dai J
Jiang Z
Hou W
Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity
description Xiaolong Tang,1,2,* Yong Liang,3,* Yongqiang Zhu,1,4,* Chunmei Xie,5 Aixia Yao,1 Li Chen,1 Qinglin Jiang,1 Tingting Liu,1 Xiaoyu Wang,1 Yunyun Qian,1 Jia Wei,1 Wenxuan Ni,1 Jingjing Dai,1 Zhenyou Jiang,6,7,* Wei Hou2,* 1Clinical Laboratory, Huainan First People’s Hospital and First Affiliated Hospital of Medical College, Anhui University of Science & Technology, Huainan, 2State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, 3Clinical Laboratory, Huai’an Hospital Affiliated of Xuzhou Medical College, Huaian, 4Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 5School of Biotechnology, Southern Medical University, 6Department of Microbiology and Immunology, School of Medicine, 7Guangdong Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood–brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])–PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection. Keywords: drug delivery, nanocarrier, amphotericin B, blood–brain barrier, transferrin receptor
format article
author Tang X
Liang Y
Zhu Y
Xie C
Yao A
Chen L
Jiang Q
Liu T
Wang X
Qian Y
Wei J
Ni W
Dai J
Jiang Z
Hou W
author_facet Tang X
Liang Y
Zhu Y
Xie C
Yao A
Chen L
Jiang Q
Liu T
Wang X
Qian Y
Wei J
Ni W
Dai J
Jiang Z
Hou W
author_sort Tang X
title Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity
title_short Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity
title_full Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity
title_fullStr Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity
title_full_unstemmed Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity
title_sort anti-transferrin receptor-modified amphotericin b-loaded pla–peg nanoparticles cure candidal meningitis and reduce drug toxicity
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/e655dafc621b4617aced508bf92bf5ab
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