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Novel Inhalable Ciprofloxacin Dry Powders for Bronchiectasis Therapy: Mannitol–Silk Fibroin Binary Microparticles with High-Payload and Improved Aerosolized Properties

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Abstract

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease associated with the high morbidity and mortality. Long-term intermittent therapy by inhalable antibiotics has recently emerged as an effective approach for NCFB treatment. However, the effective delivery of antibiotics to the lung requires administering a high dose to the site of infection. Herein, we investigated the novel inhalable silk-based microparticles as a promising approach to deliver high-payload ciprofloxacin (CIP) for NCFB therapy. Silk fibroin (SF) was applied to improve drug-payload and deposit efficiency of the dry powder particles. Mannitol was added as a mucokinetic agent. The dry powder inhaler (DPI) formulations of CIP microparticles were evaluated in vitro in terms of the aerodynamic performance, particle size distribution, drug loading, morphology, and their solid state. The optimal formulation (highest drug loading, 80%) exhibited superior aerosolization performance in terms of fine particle fraction (45.04 ± 0.84%), emitted dose (98.10 ± 1.27%), mass median aerodynamic diameter (3.75 ± 0.03 μm), and geometric standard deviation (1.66 ± 0.10). The improved drug loading was due to the electrostatic interactions between the SF and CIP by adsorption, and the superior aerosolization efficiency would be largely attributed to the fluffy and porous cotton-like property and low-density structure of SF. The presented results indicated the novel inhalable silk-based DPI microparticles of CIP could provide a promising strategy for the treatment of NCFB.

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Funding

This work was supported by National Natural Science Foundation of China (Grant No. 81503001), Guangdong Natural Science Foundation (Grant No. 2016A030313330), Guangdong Province Science and Technology Plan Project Public Welfare Fund and Ability Construction Project (Grant No. 2017A020215081, Grant No. 2016A020215069, Grant No. 2016A020215063), the Science and Technology Foundation of Guangzhou (Grant No.201707010103), and Yixian Scientific Research Project Set Sail (Grant No. YXQH201706).

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Author notes

  1. Chunxia Liu and Ling Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, No.132 Xingang West Road, Haizhu District, Guangzhou, 510120, People’s Republic of China

    Chunxia Liu, Li Lv, Xiaoxia Yu & Guocheng Li

  2. Department of Pharmacy, Zengcheng District People’s Hospital of Guangzhou, Guangming East Road, Zengcheng District, Guangzhou, 511300, People’s Republic of China

    Chunxia Liu, Qiaoli Wu & Guocheng Li

  3. School of Pharmaceutical Sciences, Sun Yat-Sen University, No.132 Waihuandong Road, University Town, Guangzhou, 510006, People’s Republic of China

    Ling Lin, Zhengwei Huang, Guilan Quan & Chuanbin Wu

  4. College of Pharmacy, Shenyang Pharmaceutical University, Benxi, 117004, People’s Republic of China

    Junhuang Jiang

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  1. Chunxia Liu
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Correspondence to Guilan Quan or Guocheng Li.

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Liu, C., Lin, L., Huang, Z. et al. Novel Inhalable Ciprofloxacin Dry Powders for Bronchiectasis Therapy: Mannitol–Silk Fibroin Binary Microparticles with High-Payload and Improved Aerosolized Properties. AAPS PharmSciTech 20, 85 (2019). https://doi.org/10.1208/s12249-019-1291-5

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