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评估一种新型口服脂质体两性霉素B制剂对烟曲霉感染大鼠给药后的抗真菌活性。

Assessing the antifungal activity of a new oral lipid-based amphotericin B formulation following administration to rats infected with Aspergillus fumigatus.

作者信息

Risovic Verica, Rosland Mike, Sivak Olena, Wasan Kishor M, Bartlett Karen

机构信息

Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

Drug Dev Ind Pharm. 2007 Jul;33(7):703-7. doi: 10.1080/03639040601077349.

Abstract

The purpose of this study was to assess the antifungal activity of a new oral amphotericin B (AmpB) lipid-based formulation following administration to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (2.1-2.5 x 10(7) colony forming units [CFU]) were injected via the jugular vein; 48h later male albino Sprague-Dawley rats (350-400 g) were administered either a single oral dose of AmpB incorporated into Peceol (50 mg AmpB/kg), physiologic saline (nontreated controls) or Peceol alone (vehicle control) once daily for 4 days. To assess antifungal activity Brain, Lung, Heart, Liver, Spleen and Kidney sections were homogenized with normal saline (1 mL/g of tissue) and a 0.1-mL aliquot was spread plated onto a Sabourand dextrose agar plate. The plates were incubated for 48 hr at 37 degrees C, at which time the number of fungal CFU were determined and corrected for tissue weight. In addition, plasma galactomannan antigen concentrations were determined. Data was reported as mean +/- standard error of the mean. The AmpB-Peceol oral formulation significantly decreased total fungal CFU concentrations recovered in all the organs added together, brain CFU concentrations, spleen CFU concentrations and plasma galactomannan antigen concentrations compared to baseline. No significant differences in lung, heart, liver and kidney CFU concentrations between treatment and control groups were observed. Peceol vehicle control did not exhibit any antifungal activity. These findings suggest that a new oral lipid-based formulation of AmpB incorporated into Peceol can significantly decrease brain and spleen CFU concentrations and plasma galactomannan antigen concentrations compared to non-treated controls.

摘要

本研究的目的是评估一种新型口服两性霉素B(AmpB)脂质体制剂在给感染烟曲霉的大鼠给药后的抗真菌活性。通过颈静脉注射烟曲霉接种物(2.1 - 2.5×10⁷菌落形成单位[CFU]);48小时后,对雄性白化Sprague-Dawley大鼠(350 - 400克)每天口服一次掺入Peceol的AmpB单剂量(50毫克AmpB/千克)、生理盐水(未处理对照组)或仅Peceol(载体对照组),持续4天。为了评估抗真菌活性,将脑、肺、心脏、肝脏、脾脏和肾脏组织切片用生理盐水(1毫升/克组织)匀浆,取0.1毫升等分试样铺在沙氏葡萄糖琼脂平板上。平板在37℃下孵育48小时,此时测定真菌CFU数量并根据组织重量进行校正。此外,还测定了血浆半乳甘露聚糖抗原浓度。数据报告为平均值±平均标准误差。与基线相比,AmpB - Peceol口服制剂显著降低了所有器官中回收的总真菌CFU浓度、脑CFU浓度、脾脏CFU浓度和血浆半乳甘露聚糖抗原浓度。治疗组和对照组之间在肺、心脏、肝脏和肾脏CFU浓度方面未观察到显著差异。Peceol载体对照组未表现出任何抗真菌活性。这些发现表明,与未处理的对照组相比,掺入Peceol的新型口服脂质体AmpB制剂可显著降低脑和脾脏CFU浓度以及血浆半乳甘露聚糖抗原浓度。

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