Preparation, characterization, and antibacterial activity of tigecycline-loaded, ultrasound-activated microbubbles

Abstract

Central nervous system infectious disease caused by the multidrug-resistant Acinetobacter baumannii (AB) seriously threatens human life in clinic. Tigecycline has good sensitivity in killing AB, but due to its wide tissue distribution and blood-brain barrier, concentration in cerebrospinal fluid is low, therefore, the clinical effect is limited. Herein, we designed micro-bubbled tigecycline, aimed to enhance its anti-MDRAB effects under ultrasound. The lipid microbubbles with different ratios of lipids to drugs (a ratio of 10:1, 20:1, and 40:1) were prepared by the mechanical shaking method. The morphology, zeta potential and particle size of microbubbles were tested to screen out the much better formulation. Encapsulation efficiency and drug loading amount were determined by ultracentrifugation combined with high-performance liquid chromatography. Then the in vitro antibacterial activity against AB was conducted using the selected ultrasound-activated microbubble. Results showed the selected microbubbles with high encapsulation efficiency and good stability. The mechanical shaking method is feasible for preparation of drug-loaded and ultrasound-activated lipid microbubbles. Using 0.2 mg/mL microbubbles, combined with 1 MHz, 2.5 W/cm² and 1 min of ultrasound exhibited a potent anit-AB in vitro. This study indicates that tigecycline treatment in form of ultrasound-activated microbubble is a promising strategy against AB infections.

Keywords:

• Tigecycline
• ultrasound
• lipid microbubbles
• in vitro antibacterial activity
• Acinetobacter baumannii

Acknowledgement

Phospholipid materials, including DSPC, DPPG-Na and DSPE-PEG₂₀₀₀ used in this study were gift from Jiangsu Southeast Nanomaterials Co., LTD., China. The sincere acknowledgement and best regards are attached here specially.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Funding acquisition: Yanyan Xu. Supervision: Jilai Tian. Project administration: Haixiang Wang. Investigation: Yanyan Xu, Yajun Ren and Yanyan Zhu. Methodology: Xiayan Zhang. Resources: Zhenbo Wu. Original draft preparation: Ziwei Mei and Jieru Hu. Writing – review & editing: Haixiang Wang and Jilai Tian. Validation: Yuhe Li and Xiaoyu Chen. Data curation: Ni Huang and Xi Xu.

Additional information

Funding

This work was supported by Zhejiang Provincial Natural Science Foundation of China [grant number LY18H300007], [grant number LYY19H280004]; High Level Talented Person Cultivating Program of Lishui Science and Technology Bureau [grant number 2018RC06]; and Research Fund of Wu Jieping Medical Foundation, Clinical Pharmacy Branch of Chinese Medical Association [grant number LCYX-Q014].