Cargando…

Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans

Recent decades have seen a significant increase in invasive fungal infections, resulting in unacceptably high mortality rates. Anidulafungin (AN) is the newest echinocandin and appears to have several advantages over existing antifungals. However, its poor water solubility and burdensome route of ad...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yu, Liu, Yan-Chao, Chen, Si-Min, Zong, Hui, Hou, Wei-Tong, Qiu, Xi-Ran, Guo, Shi-Yu, Sun, Yu-Fang, Jiang, Yuan-Ying, An, Mao-Mao, Shen, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712755/
https://www.ncbi.nlm.nih.gov/pubmed/34970244
http://dx.doi.org/10.3389/fmicb.2021.788442
_version_ 1784623624301314048
author Zhang, Yu
Liu, Yan-Chao
Chen, Si-Min
Zong, Hui
Hou, Wei-Tong
Qiu, Xi-Ran
Guo, Shi-Yu
Sun, Yu-Fang
Jiang, Yuan-Ying
An, Mao-Mao
Shen, Hui
author_facet Zhang, Yu
Liu, Yan-Chao
Chen, Si-Min
Zong, Hui
Hou, Wei-Tong
Qiu, Xi-Ran
Guo, Shi-Yu
Sun, Yu-Fang
Jiang, Yuan-Ying
An, Mao-Mao
Shen, Hui
author_sort Zhang, Yu
collection PubMed
description Recent decades have seen a significant increase in invasive fungal infections, resulting in unacceptably high mortality rates. Anidulafungin (AN) is the newest echinocandin and appears to have several advantages over existing antifungals. However, its poor water solubility and burdensome route of administration (i.e., repeated, long-term intravenous infusions) have limited its practical use. The objective of this study was to develop anidulafungin-loaded Human Serum Albumin (HSA) nanoparticles (NP) so as to increase both its solubility and antifungal efficacy. HSA was reduced using SDS and DTT, allowing liberation of free thiols to form the intermolecular disulfide network and nanoassembly. Reduced HSA was then added to MES buffer (0.1 M, pH 4.8) and magnetically stirred at 350 rpm and 25°C with AN (m/m 50:1) for 2 h to form nanoparticles (AN NP). We next performed routine antifungal susceptibility testing of Candida strains (n = 31) using Clinical and Laboratory Standards Institute (CLSI) methodologies. Finally, the in vivo efficacy of both AN and AN NP was investigated in a murine model of invasive infection by one of the most common fungal species—C. albicans. The results indicated that our carrier formulations successfully improved the water solubility of AN and encapsulated AN, with the latter having a particle size of 29 ± 1.5 nm with Polymer dispersity index (PDI) equaling 0.173 ± 0.039. In vitro AN NP testing revealed a stronger effect against Candida species (n = 31), with Minimum Inhibitory Concentration (MIC) values 4- to 32-fold lower than AN alone. In mice infected with Candida and having invasive candidiasis, we found that AN NP prolonged survival time (P < 0.005) and reduced fungal burden in kidneys compared to equivalent concentrations of free drug (P < 0.0001). In conclusion, the anidulafungin nanoparticles developed here have the potential to improve drug administration and therapeutic outcomes for individuals suffering from fungal diseases.
format Online
Article
Text
id pubmed-8712755
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87127552021-12-29 Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans Zhang, Yu Liu, Yan-Chao Chen, Si-Min Zong, Hui Hou, Wei-Tong Qiu, Xi-Ran Guo, Shi-Yu Sun, Yu-Fang Jiang, Yuan-Ying An, Mao-Mao Shen, Hui Front Microbiol Microbiology Recent decades have seen a significant increase in invasive fungal infections, resulting in unacceptably high mortality rates. Anidulafungin (AN) is the newest echinocandin and appears to have several advantages over existing antifungals. However, its poor water solubility and burdensome route of administration (i.e., repeated, long-term intravenous infusions) have limited its practical use. The objective of this study was to develop anidulafungin-loaded Human Serum Albumin (HSA) nanoparticles (NP) so as to increase both its solubility and antifungal efficacy. HSA was reduced using SDS and DTT, allowing liberation of free thiols to form the intermolecular disulfide network and nanoassembly. Reduced HSA was then added to MES buffer (0.1 M, pH 4.8) and magnetically stirred at 350 rpm and 25°C with AN (m/m 50:1) for 2 h to form nanoparticles (AN NP). We next performed routine antifungal susceptibility testing of Candida strains (n = 31) using Clinical and Laboratory Standards Institute (CLSI) methodologies. Finally, the in vivo efficacy of both AN and AN NP was investigated in a murine model of invasive infection by one of the most common fungal species—C. albicans. The results indicated that our carrier formulations successfully improved the water solubility of AN and encapsulated AN, with the latter having a particle size of 29 ± 1.5 nm with Polymer dispersity index (PDI) equaling 0.173 ± 0.039. In vitro AN NP testing revealed a stronger effect against Candida species (n = 31), with Minimum Inhibitory Concentration (MIC) values 4- to 32-fold lower than AN alone. In mice infected with Candida and having invasive candidiasis, we found that AN NP prolonged survival time (P < 0.005) and reduced fungal burden in kidneys compared to equivalent concentrations of free drug (P < 0.0001). In conclusion, the anidulafungin nanoparticles developed here have the potential to improve drug administration and therapeutic outcomes for individuals suffering from fungal diseases. Frontiers Media S.A. 2021-12-14 /pmc/articles/PMC8712755/ /pubmed/34970244 http://dx.doi.org/10.3389/fmicb.2021.788442 Text en Copyright © 2021 Zhang, Liu, Chen, Zong, Hou, Qiu, Guo, Sun, Jiang, An and Shen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhang, Yu
Liu, Yan-Chao
Chen, Si-Min
Zong, Hui
Hou, Wei-Tong
Qiu, Xi-Ran
Guo, Shi-Yu
Sun, Yu-Fang
Jiang, Yuan-Ying
An, Mao-Mao
Shen, Hui
Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans
title Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans
title_full Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans
title_fullStr Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans
title_full_unstemmed Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans
title_short Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans
title_sort evaluation of the in vitro activity and in vivo efficacy of anidulafungin-loaded human serum albumin nanoparticles against candida albicans
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712755/
https://www.ncbi.nlm.nih.gov/pubmed/34970244
http://dx.doi.org/10.3389/fmicb.2021.788442
work_keys_str_mv AT zhangyu evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT liuyanchao evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT chensimin evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT zonghui evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT houweitong evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT qiuxiran evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT guoshiyu evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT sunyufang evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT jiangyuanying evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT anmaomao evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans
AT shenhui evaluationoftheinvitroactivityandinvivoefficacyofanidulafunginloadedhumanserumalbuminnanoparticlesagainstcandidaalbicans