解锁无法达到的:为下一代Posaconazole疗法提供电离体热体
Ankita N Yawalkar1, Kshitija M Phatak1, Sushant S Sole2
1Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology Elite Status and Center of Excellence - Govt. of Maharashtra, University under Section 3 of UGC Act - 1956, Matunga (E), Mumbai, Maharashtra 400019, India.
新的ThermoSomes封装了Posaconazole (PCZ) 用于侵入性真菌感染 (IFI). 阴离子热素体显示增强的真菌细胞吸收和改善的药理动力学,提供一个可扩展和具有成本效益的IFI治疗替代方案.
科学领域:
- 纳米技术 纳米技术
- 制药科学 制药科学
- 菌类学 菌类学是指菌类学.
背景情况:
- 侵袭性真菌感染 (IFI) 由于发病率和抗真菌耐药性日益增加,构成了全球重大健康挑战.
- 目前的抗真菌疗法存在诸如毒性,快速清除和新兴耐药性等局限性.
- 现有的基于脂质的配方虽然在临床上取得了成功,但面临着制造和成本障碍.
研究的目的:
- 开发一种新的,无溶剂的,基于纳米技术的Posaconazole (PCZ) 配方,称为ThermoSomes,用于治疗FI.
- 通过设计质量 (QbD) 原则优化PCZ-ThermoSomes,并评估其作为可扩展和具有成本效益的治疗选择的潜力.
主要方法:
- 使用无溶剂方法开发了ThermoSomes,即封装PCZ的双层脂质囊泡.
- 在 silico 中,药物辅助剂相互作用,体外验证和 QbD 用于配方优化.
- 对比性研究评估了菌细胞内部化,药理动力学和活体疗效在小鼠候群病模型.
主要成果:
- 与中性和阳离子配方相比,阴离子热素体显示真菌细胞内化率增加了6倍.
- 药物动力学分析显示,AUC0-48h增加了4.68倍,t1/2增加了1.37倍.
- 在体内研究表明,PCZ-ThermoSomes与市场上提供的解决方案相比,在关键器官中的真菌负担减少了约2倍.
结论:
- PCZ-ThermoSomes代表了一种安全,稳定,无毒和有效的纳米技术驱动的IFI治疗替代方案.
- 这种配方克服了传统疗法的局限性,通过增强药物输送到目标器官并保持治疗度来克服这些局限性.
- 开发的ThermoSomes提供了一个可扩展和具有成本效益的解决方案,扩大了Posaconazole在管理FI的治疗范围.
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