Efficacy of CG(3)R(6)TAT nanoparticles self-assembled from a novel antimicrobial peptide for the treatment of Candida albicans meningitis in rabbits.

Abstract

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 CG(3)R(6)TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model of candidal meningitis.

METHODS:

In vitro activity of CG(3)R(6)TAT nanoparticles against Candida albicans was assessed by determining the minimum inhibitory concentration and kill-time curves. In vivo, intravenous treatment with CG(3)R(6)TAT 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 complete- ly 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 CG(3)R(6)TAT 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 CG(3)R(6)TAT 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 CG(3)R(6)TAT treatment (p = 0.001, vs. control).

CONCLUSION:

This study suggests that CG(3)R(6)TAT nanoparticles may be a promising therapeutic agent for candidal meningitis.

• Authors: Kaijin Xu, Huaying Wang, Lihong Liu, Wei Xu, Jifang Sheng, Weimin Fan, Yi-Yan Yang, Lanjuan Li
• Journal: Chemotherapy (Chemotherapy) Vol. 57 Issue 5 Pg. 417-25 ( 2011) ISSN: 1421-9794 [Electronic] Switzerland
• PMID: 22024735 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Antimicrobial Cationic Peptides

Topics

• Animals
• Antimicrobial Cationic Peptides (administration & dosage, pharmacology)
• Candida albicans (drug effects)
• Candidiasis (drug therapy, pathology)
• Dose-Response Relationship, Drug
• Male
• Meningitis, Fungal (drug therapy, pathology)
• Mice
• Mice, Inbred ICR
• Microbial Sensitivity Tests
• Nanoparticles (administration & dosage, chemistry)
• Rabbits