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Pharmaceutics
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Inhaled Treatment of Respiratory Infections, 2nd Edition
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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: 28 February 2025 | Viewed by 6164

Special Issue Editors

Dr. Philip Chi Lip Kwok

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals
Dr. Michael Yee Tak Chow

E-Mail Website
Guest Editor
Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, 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

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

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Related Special Issue

Published Papers (3 papers)

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Research

16 pages, 5063 KiB  
Article
Respiratory Delivery of Lacticaseibacillus rhamnosus GG by Vibrating-Mesh and Jet Nebulisation
by Alex Seungyeon Byun, Luis Vitetta, Hak-Kim Chan and Philip Chi Lip Kwok
Pharmaceutics 2024, 16(10), 1326; https://doi.org/10.3390/pharmaceutics16101326 - 14 Oct 2024
Viewed by 1614
Abstract
Background: The use of probiotic bacteria to improve lung health has been gaining interest. Although the oral delivery of probiotics and their effects are well documented, there is currently limited knowledge on the respiratory delivery of probiotics. Objectives: This study aimed to investigate [...] Read more.
Background: The use of probiotic bacteria to improve lung health has been gaining interest. Although the oral delivery of probiotics and their effects are well documented, there is currently limited knowledge on the respiratory delivery of probiotics. Objectives: This study aimed to investigate whether nebulisation is suitable for delivering Lacticaseibacillus rhamnosus GG (LGG) into the lungs for the potential treatment of bacterial pulmonary infections. Methods: It compared the dose output and aerosol performance of a vibrating-mesh nebuliser (VMN) and a jet nebuliser (JN) in nebulising LGG suspended in de Man Rogosa Sharpe (MRS) broth, phosphate-buffered saline (PBS), or normal saline (0.9% w/v sodium chloride in water). Results: The VMN consistently produced a higher output than the JN for all liquid media, indicating that VMN was more efficient. The fine-particle fractions of both nebulisers were comparable for a given medium. The highest fine-particle fraction was achieved with LGG suspended in MRS broth for both nebulisers (20.5 ± 2.8% for VMN; 18.7 ± 3.4% for JN). This suggests that the aerosol performance of nebulised probiotics may depend on the medium in which the probiotic bacteria were suspended. Conclusions: Therefore, this study demonstrated that the nebulisation efficiency of LGG depended on the nebuliser type and liquid medium of the probiotic suspension. Full article
(This article belongs to the Special Issue Inhaled Treatment of Respiratory Infections, 2nd Edition)
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18 pages, 8249 KiB  
Article
Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A Randomised, Double-Blinded, Placebo-Controlled Trial
by Stephen Winchester, Alex Castellarnau, Kashif Jabbar, Meera Nadir, Kapila Ranasinghe, Xavier Masramon, George R. Kinghorn, Isaac John and Jeremy R. A. Paull
Pharmaceutics 2024, 16(9), 1173; https://doi.org/10.3390/pharmaceutics16091173 - 6 Sep 2024
Viewed by 1817
Abstract
Background/Objectives: Dendrimer-based astodrimer sodium nasal spray was assessed for its ability to reduce SARS-CoV-2 load in outpatients with COVID-19, which remains a severe illness for vulnerable groups. Methods: This was a randomised, double-blind, placebo-controlled clinical investigation evaluating the efficacy of astodrimer nasal spray [...] Read more.
Background/Objectives: Dendrimer-based astodrimer sodium nasal spray was assessed for its ability to reduce SARS-CoV-2 load in outpatients with COVID-19, which remains a severe illness for vulnerable groups. Methods: This was a randomised, double-blind, placebo-controlled clinical investigation evaluating the efficacy of astodrimer nasal spray in reducing SARS-CoV-2 viral burden in the nasopharynx of outpatients with COVID-19. Non-hospitalised adults with SARS-CoV-2 infection were randomised 1:1 to astodrimer or placebo four times daily from Day 1 to Day 7. Nasopharyngeal swabs for SARS-CoV-2 load determination were self-obtained daily from Day 1 to Day 8. The primary endpoint was an area under the curve of SARS-CoV-2 RNA copies/mL through Day 8 (vAUCd1–8). The primary analysis population was the modified intent-to-treat population (mITT: all randomised participants exposed to the study treatment who had at least one post-baseline viral load determination). Safety analyses included all randomised participants exposed to the study treatment. Study registration: ISRCTN70449927; Results: 231 participants were recruited between 9 January and 20 September 2023. The safety population comprised 109 and 113 participants randomised to astodrimer and placebo, respectively, with 96 and 101 participants in the mITT. Astodrimer sodium nasal spray reduced the SARS-CoV-2 burden (vAUCd1–8) vs. placebo in non-hospitalised COVID-19 patients aged 16 years and over (−1.2 log10 copies/mL × Day). The reduction in SARS-CoV-2 load was statistically significant in those aged 45 years and older (−3.7, p = 0.017) and the effect increased in older age groups, including in those aged 65 years and older (−7.3, p = 0.005). Astodrimer sodium nasal spray increased the rate of viral clearance and helped alleviate some COVID-19 symptoms, especially loss of sense of smell. Overall, 31 participants (14%) had ≥1 adverse event (AE). Four AEs were deemed possibly related to treatment. Most AEs were of mild severity and occurred at similar rates in both treatment arms. Conclusions: Astodrimer nasal spray reduces viral burden and accelerates viral clearance, especially in older populations, and is well tolerated. Full article
(This article belongs to the Special Issue Inhaled Treatment of Respiratory Infections, 2nd Edition)
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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
Cited by 1 | Viewed by 1721
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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