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

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 ther...

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Autores principales: Tang, Xiaolong, Liang, Yong, Zhu, Yongqiang, Xie, Chunmei, Yao, Aixia, Chen, Li, Jiang, Qinglin, Liu, Tingting, Wang, Xiaoyu, Qian, Yunyun, Wei, Jia, Ni, Wenxuan, Dai, Jingjing, Jiang, Zhenyou, Hou, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
Materias:
Original Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599718/
https://www.ncbi.nlm.nih.gov/pubmed/26491294
http://dx.doi.org/10.2147/IJN.S84656
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author Tang, Xiaolong
Liang, Yong
Zhu, Yongqiang
Xie, Chunmei
Yao, Aixia
Chen, Li
Jiang, Qinglin
Liu, Tingting
Wang, Xiaoyu
Qian, Yunyun
Wei, Jia
Ni, Wenxuan
Dai, Jingjing
Jiang, Zhenyou
Hou, Wei
author_facet Tang, Xiaolong
Liang, Yong
Zhu, Yongqiang
Xie, Chunmei
Yao, Aixia
Chen, Li
Jiang, Qinglin
Liu, Tingting
Wang, Xiaoyu
Qian, Yunyun
Wei, Jia
Ni, Wenxuan
Dai, Jingjing
Jiang, Zhenyou
Hou, Wei
author_sort Tang, Xiaolong
collection PubMed
description 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.
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spelling pubmed-45997182015-10-21 Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity Tang, Xiaolong Liang, Yong Zhu, Yongqiang Xie, Chunmei Yao, Aixia Chen, Li Jiang, Qinglin Liu, Tingting Wang, Xiaoyu Qian, Yunyun Wei, Jia Ni, Wenxuan Dai, Jingjing Jiang, Zhenyou Hou, Wei Int J Nanomedicine Original Research 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. Dove Medical Press 2015-10-05 /pmc/articles/PMC4599718/ /pubmed/26491294 http://dx.doi.org/10.2147/IJN.S84656 Text en © 2015 Tang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Tang, Xiaolong
Liang, Yong
Zhu, Yongqiang
Xie, Chunmei
Yao, Aixia
Chen, Li
Jiang, Qinglin
Liu, Tingting
Wang, Xiaoyu
Qian, Yunyun
Wei, Jia
Ni, Wenxuan
Dai, Jingjing
Jiang, Zhenyou
Hou, Wei
Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599718/
https://www.ncbi.nlm.nih.gov/pubmed/26491294
http://dx.doi.org/10.2147/IJN.S84656
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