Inhalable tobramycin EEG powder formulation for treating Pseudomonas aeruginosa-induced lung infection.

Autor: Pangeni R; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA., Poudel S; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA., Momin MAM; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA., Farkas D; Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA., Dalton C; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA., Hall F; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA., Kang JD; Division of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA; Stravitz-Sanyal Institute for Liver Disease & Metabolic Health, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA., Hylemon P; Division of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA., Longest W; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA; Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA., Hindle M; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA., Xu Q; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA; Department of Ophthalmology, Massey Cancer Center, Center for Pharmaceutical Engineering, and Institute for Structural Biology, Drug Discovery & Development (ISB3D), Virginia Commonwealth University, Richmond, VA, USA. Electronic address: qxu@vcu.edu.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Sep 05; Vol. 662, pp. 124504. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.1016/j.ijpharm.2024.124504
Abstrakt: Pulmonary delivery of antibiotics is an effective strategy in treating bacterial lung infection for cystic fibrosis patients, by achieving high local drug concentrations and reducing overall systemic exposure compared to systemic administration. However, the inherent anatomical lung defense mechanisms, formulation characteristics, and drug-device combination determine the treatment efficacy of the aerosol delivery approach. In this study, we prepared a new tobramycin (Tobi) dry powder aerosol using excipient enhanced growth (EEG) technology and evaluated the in vitro and in vivo aerosol performance. We further established a Pseudomonas aeruginosa-induced lung infection rat model using an in-house designed novel liquid aerosolizer device. Notably, novel liquid aerosolizer yields comparable lung infection profiles despite administering 3-times lower P. aeruginosa CFU per rat in comparison to the conventional intratracheal administration. Dry powder insufflator (e.g. Penn-Century DP-4) to administer small powder masses to experimental animals is no longer commercially available. To address this gap, we developed a novel rat air-jet dry powder insufflator (Rat AJ DPI) that can emit 68-70 % of the loaded mass for 2 mg and 5 mg of Tobi-EEG powder formulations, achieving a high rat lung deposition efficiency of 79 % and 86 %, respectively. Rat AJ DPI can achieve homogenous distribution of Tobi EEG powder formulations at both loaded mass (2 mg and 5 mg) over all five lung lobes in rats. We then demonstrated that Tobi EEG formulation delivered by Rat AJ DPI can significantly decrease CFU counts in both trachea and lung lobes at 2 mg (p < 0.05) and 5 mg (p < 0.001) loaded mass compared to the untreated P. aeruginosa-infected group. Tobi EEG powder formulation delivered by the novel Rat AJ DPI showed excellent efficiencies in substantially reducing the P. aeruginosa-induced lung infection in rats.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael Hindle, Worth Longest has patent EXCIPIENT ENHANCED GROWTH (EEG) OF NANOPARTICLE AEROSOLSTO ENABLE IMPROVED PULMONARY TARTETING AND RETENTION issued to Quench Medical. Michael Hindle, Worth Longest has patent DRY POWDER INHALER (DPI) DESIGN FOR PRODUCING AEROSOLS WITHHIGH FINE PARTICLE FRACTIONS issued to Quench Medical. Michael Hindle, Worth Longest, Dale Farkas has patent Dry powder inhalers and interfaces for improved aerosol delivery to children pending to Virginia Commonwealth University. Michael Hindle, Worth Longest, Dale Farkas has patent Devices, systems, and methods for dry powder therapies pending to Virginia Commonwealth University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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