Inhaled Treatment of Respiratory Infections, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 1256

Special Issue Editors


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Guest Editor
Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, Pharmacy and Bank Building A15, The University of Sydney, Sydney, NSW 2006, Australia
Interests: pulmonary delivery; aerosols; inhalation; particle engineering; formulation; physicochemical characterisation; electrostatics
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Guest Editor
UCL School of Pharmacy, University College London, London WC1E 6BT, UK
Interests: bacteriophage; biopharmaceutics; gene delivery; inhalation; particle engineering; pulmonary drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Respiratory infections are conventionally treated with oral or intravenous antimicrobials (antibiotics, antifungals, antivirals). However, these routes of administration are not ideal because the required drugs are systemically delivered rather than being targeted to the respiratory tract. Higher doses may also be needed to achieve sufficiently high drug concentrations in the lungs, which may consequently cause more adverse effects. On the other hand, the drugs can be delivered efficiently into the airways as inhaled aerosols. Lower doses can then be used to attain relatively high local concentrations. There are specific challenges to the development of inhaled formulations, such as optimising their physicochemical stability and aerosol performance. In addition, antimicrobial resistance is an urgent global public health issue. Novel strategies are required to overcome these problems.

This Special Issue, Inhaled Treatment of Respiratory Infections—Volume II, will focus on recent advances in treating respiratory infections with inhaled formulations.

Dr. Philip Chi Lip Kwok
Dr. Michael Y. T. Chow
Guest Editors

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Keywords

  • respiratory infections
  • inhalation
  • aerosols
  • pulmonary drug delivery
  • antimicrobials

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Published Papers (1 paper)

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Research

15 pages, 11190 KiB  
Article
Tobramycin Reduces Pulmonary Toxicity of Polymyxin B via Inhibiting the Megalin-Mediated Drug Uptake in the Human Lung Epithelial Cells
by Maizbha Uddin Ahmed, Jian Li and Qi (Tony) Zhou
Pharmaceutics 2024, 16(3), 389; https://doi.org/10.3390/pharmaceutics16030389 - 12 Mar 2024
Viewed by 832
Abstract
Accumulation of polymyxins in the lung epithelial cells can lead to increased mitochondrial oxidative stress and pulmonary toxicity. Aminoglycosides and polymyxins are used, via intravenous and pulmonary delivery, against multidrug-resistant Gram-negative pathogens. Our recent in vitro and animal studies demonstrated that the co-administration [...] Read more.
Accumulation of polymyxins in the lung epithelial cells can lead to increased mitochondrial oxidative stress and pulmonary toxicity. Aminoglycosides and polymyxins are used, via intravenous and pulmonary delivery, against multidrug-resistant Gram-negative pathogens. Our recent in vitro and animal studies demonstrated that the co-administration of polymyxins with aminoglycosides decreases polymyxin-induced pulmonary toxicity. The aim of this study was to investigate the in vitro transport and uptake of polymyxin B and tobramycin in human lung epithelial Calu-3 cells and the mechanism of reduced pulmonary toxicity resulting from this combination. Transport, intracellular localization, and accumulation of polymyxin B and tobramycin were investigated using doses of 30 mg/L polymyxin B, 70 mg/L tobramycin, and the combination of both. Adding tobramycin significantly (p < 0.05) decreased the polymyxin B-induced cytotoxicity in Calu-3 cells. The combination treatment significantly reduced the transport and uptake of polymyxin B and tobramycin in Calu-3 cells, compared to each drug alone, which supported the reduced pulmonary toxicity. We hypothesized that cellular uptake of polymyxin B and tobramycin shared a common transporter, megalin. We further investigated the megalin expression of Calu-3 cells using confocal microscopy and evaluated megalin activity using a megalin substrate, FITC-BSA, and a megalin inhibitor, sodium maleate. Both polymyxin B and tobramycin significantly inhibited FITC-BSA uptake by Calu-3 cells in a concentration-dependent manner. Sodium maleate substantially inhibited polymyxin B and tobramycin transport and cellular accumulation in the Calu-3 cell monolayer. Our study demonstrated that the significantly reduced uptake of polymyxin B and tobramycin in Calu-3 cells is attributed to the mechanism of action that determines that polymyxin B and tobramycin share a common transporter, megalin. Full article
(This article belongs to the Special Issue Inhaled Treatment of Respiratory Infections, 2nd Edition)
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