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Pharmaceutics
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Drug Delivery Systems for Respiratory Diseases
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Drug Delivery Systems for Respiratory Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (25 January 2025) | Viewed by 20938

Special Issue Editors

Dr. Mershen Govender

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Guest Editor
Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johannesburg 2193, South Africa
Interests: controlled release systems; mucosal delivery; nanotechnology; nutraceuticals; pharmaceutical microbiology; infectious diseases; oncology; biomaterials; tissue engineering; additive manufacturing and 3D bioprinting
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Yahya E. Choonara

E-Mail Website
Guest Editor
Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johannesburg 2193, South Africa
Interests: drug delivery; biomaterials; nanomedicine; computational pharmaceutics; neurotherapeutics; polymers; 3D bioprinting; pharmaceutics; pharmaceutical formulation; targeted drug therapy; ocular drug delivery; colloidal systems; tissue engineering; infectious diseases; oncology; HIV; tuberculosis; STIs; malaria; wound healing; protein/peptide therapeutics; nucleic acid delivery systems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The respiratory system is a complex environment predisposed to a number of ailments due to infections, autoimmune conditions and environmental exposure. The optimal functioning of this organ system is imperative for proper health and well-being. With the onset of the COVID-19 pandemic, a greater focus was placed on the impact of viruses on the respiratory system, as well as on the potential drug delivery platforms to treat this condition. Research into other respiratory disorders consequently decreased, despite their prevalence and impact on human health. The aim of this Special Issue is to attract original research articles and reviews focusing on advanced drug delivery platforms for the treatment of respiratory diseases. These diseases may include, amongst others, bacterial and viral infections, autoimmune conditions affecting the respiratory system, asthma, COPD, pulmonary hypertension, pulmonary fibrosis, tuberculosis and lung cancers.

Research areas may include, but are not limited to, the following:

  1. Novel synthesis of delivery systems, drug formulations and development technologies for respiratory diseases;
  2. Nanoplatforms for respiratory delivery (polymeric nanoparticles, nanoliposomes, nanomicelles, etc.);
  3. Novel theranostic platforms for respiratory diseases;
  4. Targeting of specific cell populations or intracellular targeting in the pulmonary environment;
  5. Design of advanced targeted drug delivery devices for increased dosing accuracy and reproducibility;
  6. Advanced drug delivery approaches for biopharmaceuticals including vaccines, antibiotics, nucleic acids, proteins and peptides.

I look forward to receiving your contributions.

Dr. Mershen Govender
Prof. Dr. Yahya E. Choonara
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • drug delivery
  • pulmonary
  • respiratory system
  • bacterial and viral infections
  • lung cancer
  • autoimmune conditions
  • asthma
  • COPD
  • nanosystems

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

6 pages, 170 KiB  
Editorial
Drug Delivery Systems for Respiratory Diseases: Insights into the Therapeutic Innovations for Pulmonary Administration
by Mershen Govender and Yahya E. Choonara
Pharmaceutics 2025, 17(5), 539; https://doi.org/10.3390/pharmaceutics17050539 - 22 Apr 2025
Viewed by 2481
Abstract
Respiratory issues, such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pulmonary hypertension, and respiratory infections, are amongst the most common and debilitating medical conditions experienced worldwide, affecting millions of patients annually [...] Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)

Research

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15 pages, 2240 KiB  
Article
Mesoporous Polydopamine Nano-Bowls Demonstrate a High Entrapment Efficiency and pH-Responsive Release of Paclitaxel for Suppressing A549 Lung Cancer Cell Proliferation In Vitro
by Lindokuhle M. Ngema, Shahinur Acter, Samson A. Adeyemi, Thashree Marimuthu, Mershen Govender, Wilfred Ngwa and Yahya E. Choonara
Pharmaceutics 2024, 16(12), 1536; https://doi.org/10.3390/pharmaceutics16121536 - 1 Dec 2024
Cited by 1 | Viewed by 1598
Abstract
Background: The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical [...] Read more.
Background: The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical need to develop an efficient carrier for the optimised delivery of PTX in NSCLC therapy. Methods: The present study describes the fabrication of mesoporous polydopamine (mPDA) nano-bowls via an emulsion-induced interfacial anisotropic assembly method, designed for efficient entrapment of PTX and pH-responsive release behaviour. Results: The nano-bowls depicted a typical bowl-like shape, with connecting mesoporous channels and a central hollow cavity, allowing optimal loading of PTX. The fabricated nanocarrier system, mPDA-PTX-nb, had a mean hydrodynamic bowl diameter of 200.4 ± 5.2 nm and a surface charge of −39.2 ± 1.3 mV. The entrapment efficiency of PTX within the nano-bowls was found to be 95.7%, with a corresponding release of 85.1% achieved at the acidic pH 5.9 (simulated tumour microenvironment) at 48 h. Drug release was best fitted to the Peppas–Sahlin model, indicating the involvement of both diffusion and relaxation mechanisms. Treatment with mPDA-PTX-nb significantly suppressed A549 lung cancer cell proliferation at 48 and 72 h, resulting in cell viability of 14.0% and 9.3%, respectively, at the highest concentration (100 µg/mL). Conclusions: These results highlight the potential of mPDA-PTX-nb as an effective nanocarrier for PTX, promoting enhanced anti-proliferative effects in NSCLC therapy. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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20 pages, 1817 KiB  
Article
Intratracheal Administration of Itraconazole-Loaded Hyaluronated Glycerosomes as a Promising Nanoplatform for the Treatment of Lung Cancer: Formulation, Physiochemical, and In Vivo Distribution
by Sultan Aati, Hanan O. Farouk, Marwa H. Elkarmalawy, Hanan Y. Aati, Nahla Sameh Tolba, Hossam M. Hassan, Mostafa E. Rateb and Doaa S. Hamad
Pharmaceutics 2024, 16(11), 1432; https://doi.org/10.3390/pharmaceutics16111432 - 10 Nov 2024
Cited by 2 | Viewed by 1912
Abstract
Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), [...] Read more.
Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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13 pages, 2855 KiB  
Article
The Ability of Vaping Technology to Deliver an Equivalent Respirable Dose of Beclomethasone Dipropionate Compared to Nebulization
by Cyrille Bruneau, Clément Mercier, Lara Leclerc and Jérémie Pourchez
Pharmaceutics 2024, 16(11), 1396; https://doi.org/10.3390/pharmaceutics16111396 - 30 Oct 2024
Cited by 1 | Viewed by 1455
Abstract
Background/Objectives: This study focuses on the ability of vaping technology to deliver beclomethasone dipropionate compared to nebulization. Methods: An in vitro comparison of aerosol properties in terms of respirable dose with the Glass Twin Impinger and the mass median aerodynamic diameter [...] Read more.
Background/Objectives: This study focuses on the ability of vaping technology to deliver beclomethasone dipropionate compared to nebulization. Methods: An in vitro comparison of aerosol properties in terms of respirable dose with the Glass Twin Impinger and the mass median aerodynamic diameter using the Next Generation Impactor was performed. The respirable dose delivered in a vaping drug delivery system (VDDS) puff as a function of concentration was quantified by high-pressure liquid chromatography coupled with an ultraviolet detector. Results: The mass of drug contained in a single puff of 55 mL of aerosol varied between 0.94 and 1.95 µg for a refill liquid concentration range of 400 to 1600 µg/mL. The analysis of the particle size distribution shows an advantage for a VDDS in producing smaller particles compared to nebulization (1.56 ± 0.05 µm vs. 2.30 ± 0.19 µm). In total, 81 puffs are needed to reach the dose equivalent to nebulized beclomethasone dipropionate under these specific experimental conditions, which corresponds to an aerosol duration of about 4 min (i.e., four times lower than the jet nebulizer) and a patient administration time of about 45 min (i.e., three times higher than the jet nebulizer). Conclusions: The results show the potential of vaping devices as an alternative to nebulizers for the administration of beclomethasone dipropionate in an equivalent respirable dose. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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18 pages, 3285 KiB  
Article
Development of a Formulation and In Vitro Evaluation of a Pulmonary Drug Delivery System for a Novel Janus Kinase (JAK) Inhibitor, CPL409116
by Aleksandra Rzewińska, Jakub Szlęk, Damian Dąbrowski, Ewelina Juszczyk, Katarzyna Mróz, Heikki Räikkönen, Mia Siven, Maciej Wieczorek and Przemysław Dorożyński
Pharmaceutics 2024, 16(9), 1157; https://doi.org/10.3390/pharmaceutics16091157 - 31 Aug 2024
Cited by 1 | Viewed by 2061
Abstract
The pursuit of targeted therapies for cytokine-dependent diseases has led to the discovery of Janus kinase (JAK) inhibitors, a promising class of drugs. Among them, CPL409116, a selective dual JAK and rho-associated protein kinase inhibitor (ROCK), has demonstrated potential for treating conditions such [...] Read more.
The pursuit of targeted therapies for cytokine-dependent diseases has led to the discovery of Janus kinase (JAK) inhibitors, a promising class of drugs. Among them, CPL409116, a selective dual JAK and rho-associated protein kinase inhibitor (ROCK), has demonstrated potential for treating conditions such as pulmonary fibrosis exacerbated by the COVID-19 pandemic. This study investigated the feasibility of delivering CPL409116 via inhalation, with the aim of minimizing the systemic adverse effects associated with oral administration. Two micronization methods, jet milling and spray drying, were assessed for CPL409116, with spray drying chosen for its ability to produce an amorphous form of the compound. Moreover, parameters such as the mixing energy, drug load, and force control agent significantly influenced the fine particle fraction (FPF), a critical parameter for pulmonary drug delivery. This study provides insights into optimizing the formulation parameters to enhance the delivery efficiency of CPL409116 to the lungs, offering potential for improved therapeutic outcomes in cytokine-dependent pulmonary diseases. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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11 pages, 1742 KiB  
Article
In-Line Aerosol Therapy via Nasal Cannula during Adult and Paediatric Normal, Obstructive, and Restrictive Breathing
by Marc Mac Giolla Eain and Ronan MacLoughlin
Pharmaceutics 2023, 15(12), 2679; https://doi.org/10.3390/pharmaceutics15122679 - 27 Nov 2023
Cited by 4 | Viewed by 2187
Abstract
High-flow nasal oxygen therapy is being increasingly adopted in intensive and home care settings. The concurrent delivery of aerosolised therapeutics allows for the targeted treatment of respiratory illnesses. This study examined in-line aerosol therapy via a nasal cannula to simulated adult and paediatric [...] Read more.
High-flow nasal oxygen therapy is being increasingly adopted in intensive and home care settings. The concurrent delivery of aerosolised therapeutics allows for the targeted treatment of respiratory illnesses. This study examined in-line aerosol therapy via a nasal cannula to simulated adult and paediatric models with healthy, obstructive and restrictive lung types. The Aerogen Solo vibrating mesh nebuliser was used in combination with the InspiredTM O2FLO high-flow therapy system. Representative adult and paediatric head models were connected to a breathing simulator, which replicated several different states of lung health. The aerosol delivery was quantified at the tracheal level using UV-spectrophotometry. Testing was performed at a range of supplemental gas flow rates applicable to both models. Positive end-expiratory pressure was measured pre-, during and post-nebulisation. The increases in supplemental gas flow rates resulted in a decrease in aerosol delivery, irrespective of lung health. Large tidal volumes and extended inspiratory phases were associated with the greatest aerosol delivery. Gas flow to inspiratory flow ratios of 0.29–0.5 were found to be optimum for aerosol delivery. To enhance aerosol delivery to patients receiving high-flow nasal oxygen therapy, respiratory therapists should keep supplemental gas-flow rates below the inspiratory flow of the patient. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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9 pages, 254 KiB  
Article
Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis
by José Luis Lopez-Campos, Rocio Reinoso-Arija, Marta Ferrer Galván, Auxiliadora Romero Falcón, Francisco J. Alvarez-Gutiérrez, Francisco Ortega-Ruiz and Esther Quintana-Gallego
Pharmaceutics 2023, 15(9), 2206; https://doi.org/10.3390/pharmaceutics15092206 - 26 Aug 2023
Cited by 1 | Viewed by 1974
Abstract
Background. Currently, there is a considerable degree of confusion over the dosage of inhaled medications. Here, we carried out a review of all the doses used for the devices used in inhalation therapy. Methods. We first performed a systematic search of the different [...] Read more.
Background. Currently, there is a considerable degree of confusion over the dosage of inhaled medications. Here, we carried out a review of all the doses used for the devices used in inhalation therapy. Methods. We first performed a systematic search of the different inhalation devices included on the July 2023 Spanish Ministry of Health Billing List. We then consulted the Spanish Agency for Medicines and Health Products to find the updated official label and to obtain the information on the exact composition. Results. We identified 90 unique products, of which 22 were long-acting bronchodilators (and combinations thereof) and 68 were products containing inhaled corticosteroids (ICS). Overall, 10 products with bronchodilators and 40 with ICS were marketed with the metered dose, while 11 with bronchodilators and 28 with ICS were marketed with the delivered dose. In addition, in some bronchodilators, the drug was referred to as a type of salt, whereas in others the information referred to the drug itself. Conclusions. Our data show that for each inhaled drug there may be up to four different doses and that the marketed name may refer to any of these. Clinicians must be aware of these different dosages when prescribing inhaled medications. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
13 pages, 19968 KiB  
Article
The Use of an Inspiration-Synchronized Vibrating Mesh Nebulizer for Prolonged Inhalative Iloprost Administration in Mechanically Ventilated Patients—An In Vitro Model
by Matthias Otto, Yannik Kropp, Evelyn Jäger, Michael Neumaier, Manfred Thiel, Michael Quintel and Charalambos Tsagogiorgas
Pharmaceutics 2023, 15(8), 2080; https://doi.org/10.3390/pharmaceutics15082080 - 3 Aug 2023
Cited by 1 | Viewed by 2370
Abstract
Mechanically ventilated patients suffering from acute respiratory distress syndrome (ARDS) frequently receive aerosolized iloprost. Because of prostacyclin’s short half-life, prolonged inhalative administration might improve its clinical efficacy. But, this is technically challenging. A solution might be the use of inspiration-synchronized vibrating mesh nebulizers [...] Read more.
Mechanically ventilated patients suffering from acute respiratory distress syndrome (ARDS) frequently receive aerosolized iloprost. Because of prostacyclin’s short half-life, prolonged inhalative administration might improve its clinical efficacy. But, this is technically challenging. A solution might be the use of inspiration-synchronized vibrating mesh nebulizers (VMNsyn), which achieve high drug deposition rates while showing prolonged nebulization times. However, there are no data comparing prolonged to bolus iloprost nebulization using a continuous vibrating mesh nebulizer (VMNcont) and investigating the effects of different ventilation modes on inspiration-synchronized nebulization. Therefore, in an in vitro model of mechanically ventilated adults, a VMNsyn and a VMNcont were compared in volume-controlled (VC-CMV) and pressure-controlled continuous mandatory ventilation (PC-CMV) regarding iloprost deposition rate and nebulization time. During VC-CMV, the deposition rate of the VMNsyn was comparable to the rate obtained with the VMNcont, but 10.9% lower during PC-CMV. The aerosol output of the VMNsyn during both ventilation modes was significantly lower compared to the VMNcont, leading to a 7.5 times longer nebulization time during VC-CMV and only to a 4.2 times longer nebulization time during PC-CMV. Inspiration-synchronized nebulization during VC-CMV mode therefore seems to be the most suitable for prolonged inhalative iloprost administration in mechanically ventilated patients. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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Review

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21 pages, 2576 KiB  
Review
Towards More Precise Targeting of Inhaled Aerosols to Different Areas of the Respiratory System
by Tomasz R. Sosnowski
Pharmaceutics 2024, 16(1), 97; https://doi.org/10.3390/pharmaceutics16010097 - 10 Jan 2024
Cited by 6 | Viewed by 3545
Abstract
Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in [...] Read more.
Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during the aerosolization of liquids or powders and the role of aerosol flow dynamics in the RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Through an analysis of existing technical limitations, selected strategies aimed at enhancing the effectiveness of targeted aerosol delivery to the RS have been identified and presented. These strategies also include the use of smart inhaling devices and systems with built-in AI algorithms. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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