ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Drug Metabolism and Transport

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1528905

This article is part of the Research TopicNon-Invasive Methods in Drug Metabolism and Transport: Insights from Biological Samples to Oral AdministrationView all 4 articles

Pulmonary delivery of excipient-free tobramycin DPIs for the treatment of Pseudomonas aeruginosa lung infection with CF

Provisionally accepted
Song ChengSong Cheng1,2Haozhou HuangHaozhou Huang3Zhihao ZhangZhihao Zhang1Yulong ZhangYulong Zhang1,4Mengxing LinMengxing Lin2Gang YangGang Yang2Lynda Thubelihle KanyeLynda Thubelihle Kanye1Qingzhen ZhangQingzhen Zhang5Ning XueNing Xue6Kaiqi ShiKaiqi Shi5*Bin DongBin Dong1,7*Hanhan LiHanhan Li1*
  • 1Department of Pharmaceutical Engineering, China Pharmaceutical University, Nanjing, China
  • 2Eastern Institute for Advanced Study, Eastern Institute of Technology, Ningbo, China
  • 3Courant Institute of Mathematical Sciences, New York University, New York, United States
  • 4Heart Science, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, England, United Kingdom
  • 5Suzhou Inhal Pharma Co., Ltd, Suzhou, China
  • 6Department of Computer Science, University of Nottingham Ningbo China, Ningbo, China
  • 7Engineering Research Center for Smart Pharmaceutical Manufacturing Technologies, Ministry of Education, China Pharmaceutical University, Nanjing, China

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Pseudomonas aeruginosa infection has become a widespread problem in patients with cystic fibrosis (CF). A safe and effective manufacturing method is required to produce antibiotic dry powder inhalations (DPIs) which can be effectively delivered to treat lung infections. In this study, an excipient-free tobramycin inhalable powder was prepared using spray freeze-drying (SFD) method.The mass median aerodynamic diameters (MMAD) of optimized inhalable powder prepared by SFD was 1.30 µm, and the fine particle fractions (FPF) reached 83.31%. In both in vitro and in vivo safety and activity studies, the inhalable powder showed excellent safety performance at both animal and cellular levels, with a minimum inhibitory concentration (MIC) of 0.5 µg/mL. Compared with intravenous injection, inhalation of excipient-free tobramycin inhalable powder had a better effect in the infected mouse model because of its amorphous state. This study demonstrates that excipient-free tobramycin inhalable powder with good delivery and deposition performance can be successfully obtained using the SFD method. Inhalation of excipient-free tobramycin inhalable powder has the potential to be a promising strategy for treating pulmonary infections caused by Pseudomonas aeruginosa in patients with CF.

Keywords: Dry powder inhalations (DPIs), Spray freeze drying (SFD), Tobramycin, pulmonary drug delivery, Pseudomonas aeruginosa infection

Received: 15 Nov 2024; Accepted: 19 May 2025.

Copyright: © 2025 Cheng, Huang, Zhang, Zhang, Lin, Yang, Kanye, Zhang, Xue, Shi, Dong and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Kaiqi Shi, Suzhou Inhal Pharma Co., Ltd, Suzhou, China
Bin Dong, Department of Pharmaceutical Engineering, China Pharmaceutical University, Nanjing, China
Hanhan Li, Department of Pharmaceutical Engineering, China Pharmaceutical University, Nanjing, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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