Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits

Background: Candidal meningitis is a common clinical manifestation of invasive candidiasis in neonates. The aim of this study was to evaluate the in vivo antifungal efficacy of CG3R6TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model...

Full description

Bibliographic Details
Main Authors: Xu, K., Wang, H., Liu, Lihong, Xu, W., Sheng, J., Fan, W., Yang, Y., Li, L.
Format: Journal Article
Published: Karger 2011
Online Access:http://hdl.handle.net/20.500.11937/33298
_version_ 1848753906760286208
author Xu, K.
Wang, H.
Liu, Lihong
Xu, W.
Sheng, J.
Fan, W.
Yang, Y.
Li, L.
author_facet Xu, K.
Wang, H.
Liu, Lihong
Xu, W.
Sheng, J.
Fan, W.
Yang, Y.
Li, L.
author_sort Xu, K.
building Curtin Institutional Repository
collection Online Access
description Background: Candidal meningitis is a common clinical manifestation of invasive candidiasis in neonates. The aim of this study was to evaluate the in vivo antifungal efficacy of CG3R6TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model of candidal meningitis. Methods: In vitro activity of CG3R6TAT nanoparticles against Candida albicans was assessed by determining the minimum inhibitory concentration and kill-time curves. In vivo, intravenous treatment with CG3R6TAT nanoparticles (n = 6; 0.25 mg/kg/day) or fluconazole (n = 6; 100 mg/kg/day) began 3 days after infection and continued for 11 consecutive days; the efficacy was assessed following 11 days of treatment by yeast counting in cerebrospinal fluid (CSF), the leukocyte concentrations in CSF and the histopathology of brain parenchyma. Results: At a concentration three times higher than the minimum inhibitory concentration (8.1 µmol/l), the nanoparticles completely sterilized C. albicans after 5 h of incubation. In addition, there was a significant reduction in fungal counts and leukocyte concentrations in the CSF from rabbits treated with CG3R6TAT nanoparticles or fluconazole versus those from untreated control rabbits (p < 0.05, ANCOVA). The median number of days of treatment required to sterilize CSF cultures was 8.5 days for CG3R6TAT nanoparticle therapy (p = 0.022, vs. control) and 9.7 days for fluconazole therapy (p > 0.05, vs. control). The histopathologic severity of rabbits was significantly attenuated after CG3R6TAT treatment (p = 0.001, vs. control). Conclusion: This study suggests that CG3R6TAT nanoparticles may be a promising therapeutic agent for candidal meningitis.
first_indexed 2025-11-14T08:31:58Z
format Journal Article
id curtin-20.500.11937-33298
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T08:31:58Z
publishDate 2011
publisher Karger
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-332982017-09-13T16:08:35Z Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits Xu, K. Wang, H. Liu, Lihong Xu, W. Sheng, J. Fan, W. Yang, Y. Li, L. Background: Candidal meningitis is a common clinical manifestation of invasive candidiasis in neonates. The aim of this study was to evaluate the in vivo antifungal efficacy of CG3R6TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model of candidal meningitis. Methods: In vitro activity of CG3R6TAT nanoparticles against Candida albicans was assessed by determining the minimum inhibitory concentration and kill-time curves. In vivo, intravenous treatment with CG3R6TAT nanoparticles (n = 6; 0.25 mg/kg/day) or fluconazole (n = 6; 100 mg/kg/day) began 3 days after infection and continued for 11 consecutive days; the efficacy was assessed following 11 days of treatment by yeast counting in cerebrospinal fluid (CSF), the leukocyte concentrations in CSF and the histopathology of brain parenchyma. Results: At a concentration three times higher than the minimum inhibitory concentration (8.1 µmol/l), the nanoparticles completely sterilized C. albicans after 5 h of incubation. In addition, there was a significant reduction in fungal counts and leukocyte concentrations in the CSF from rabbits treated with CG3R6TAT nanoparticles or fluconazole versus those from untreated control rabbits (p < 0.05, ANCOVA). The median number of days of treatment required to sterilize CSF cultures was 8.5 days for CG3R6TAT nanoparticle therapy (p = 0.022, vs. control) and 9.7 days for fluconazole therapy (p > 0.05, vs. control). The histopathologic severity of rabbits was significantly attenuated after CG3R6TAT treatment (p = 0.001, vs. control). Conclusion: This study suggests that CG3R6TAT nanoparticles may be a promising therapeutic agent for candidal meningitis. 2011 Journal Article http://hdl.handle.net/20.500.11937/33298 10.1159/000330855 Karger restricted
spellingShingle Xu, K.
Wang, H.
Liu, Lihong
Xu, W.
Sheng, J.
Fan, W.
Yang, Y.
Li, L.
Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits
title Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits
title_full Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits
title_fullStr Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits
title_full_unstemmed Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits
title_short Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits
title_sort efficacy of cg 3 r 6 tat nanoparticles self-assembled from a novel antimicrobial peptide for thetreatment of candida albicans meningitis in rabbits
url http://hdl.handle.net/20.500.11937/33298