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脂质体纳米粒控制环丙沙星在呼吸道上皮细胞的摄取。

Liposomal nanoparticles control the uptake of ciprofloxacin across respiratory epithelia.

机构信息

Advanced Drug Delivery Group, Faculty of Pharmacy (A15), The University of Sydney, Sydney, NSW 2006, Australia.

出版信息

Pharm Res. 2012 Dec;29(12):3335-46. doi: 10.1007/s11095-012-0827-0. Epub 2012 Jul 26.

Abstract

PURPOSE

Liposomal ciprofloxacin nanoparticles were developed to overcome the rapid clearance of antibiotics from the lungs. The formulation was evaluated for its release profile using an air interface Calu-3 cell model and further characterised for aerosol performance and antimicrobial activity.

METHODS

Liposomal and free ciprofloxacin formulations were nebulised directly onto Calu-3 bronchial epithelial cells placed in an in vitro twin-stage impinger (TSI) to assess the kinetics of release. The aerosol performance of both the liposomal and free ciprofloxacin formulation was characterised using the next generation impactor. Minimum inhibitory and bactericidal concentrations (MICs and MBCs) were determined and compared between formulations to evaluate the antibacterial activity.

RESULTS

The liposomal formulation successfully controlled the release of ciprofloxacin in the cell model and showed enhanced antibacterial activity against Pseudomonas aeruginosa. In addition, the formulation displayed a respirable aerosol fraction of 70.5 ± 2.03% of the emitted dose.

CONCLUSION

Results indicate that the in vitro TSI air interface Calu-3 model is capable of evaluating the fate of nebulised liposomal nanoparticle formulations and support the potential for inhaled liposomal ciprofloxacin to provide a promising treatment for respiratory infections.

摘要

目的

开发脂质体环丙沙星纳米粒以克服抗生素从肺部迅速清除的问题。该制剂的释放特性采用气-液界面 Calu-3 细胞模型进行评估,并进一步对其气溶胶性能和抗菌活性进行了表征。

方法

将脂质体和游离环丙沙星制剂直接雾化到置于体外双阶段冲击器(TSI)中的 Calu-3 支气管上皮细胞上,以评估释放动力学。使用下一代撞击器对脂质体和游离环丙沙星制剂的气溶胶性能进行了表征。测定并比较了两种制剂的最小抑菌浓度(MIC)和最小杀菌浓度(MBC),以评估抗菌活性。

结果

脂质体制剂成功地控制了细胞模型中环丙沙星的释放,并显示出对铜绿假单胞菌的增强抗菌活性。此外,该制剂显示出可吸入的气溶胶分数为 70.5±2.03%的发射剂量。

结论

结果表明,体外 TSI 气-液界面 Calu-3 模型能够评估雾化脂质体纳米粒制剂的命运,并支持吸入用脂质体环丙沙星作为治疗呼吸道感染的有前途的治疗方法。

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