Drug Delivery Systems for Asthma and Pulmonary 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 (31 July 2023) | Viewed by 20887

Special Issue Editors


E-Mail Website
Guest Editor
Department of Biochemistry, Faculty of Biology, Universidad Complutense, 28040 Madrid, Spain
Interests: pulmonary surfactant; lung drug delivery; nanoparticles; liposomes; drug-membrane interactions; inhaled drugs; respiratory physiology; lipid/protein interactions; membrane proteins
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
International Medical Center, University of Tsukuba Affiliated Hospital, Tsukuba 305-8576, Japan
Interests: cardiovascular immunology; ischemic insult; nanoparticle development; electron microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The effect of first-pass metabolism on orally administered medications plus the requirement of solubility to increase absorption limit the effectiveness of various drugs during treatment. For decades, asthmatics have relied on nebulization and aerosols for delivery, but advances in polymerization and nucleic acid packaging have shown promise that targeted therapies for the epithelial cells involved in asthmatic exacerbations will provide lasting relief. Other respiratory pathologies (including COVID-19) are being or could be also benefited from advanced inhalative therapies. Additionally, liposomal delivery of therapeutics could increase local and systemic bioavailability of active ingredients while reducing first-pass metabolism effects. Of particular interest is the packaging potential for biopolymers in delivering new therapies derived from monoclonal antibodies, as well as gel or film-based applications for use in the lungs.

We invite you to submit perspectives and research on the packaging of asthmatic medications and of drugs targeting other respiratory pathologies, increases in delivery efficiency and the biochemical interactions between target cells and engineered delivery systems.

Prof. Dr. Jesus Perez-Gil
Dr. Bryan Mathis
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

  • liposomes
  • nanocarrier
  • pH
  • hydrogel
  • asthma
  • polymeric scaffolds
  • encapsulation
  • solubility
  • microemulsification

Related Special Issue

Published Papers (8 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

18 pages, 3526 KiB  
Article
Beyond the Interface: Improved Pulmonary Surfactant-Assisted Drug Delivery through Surface-Associated Structures
by Cristina García-Mouton, Mercedes Echaide, Luis A. Serrano, Guillermo Orellana, Fabrizio Salomone, Francesca Ricci, Barbara Pioselli, Davide Amidani, Antonio Cruz and Jesús Pérez-Gil
Pharmaceutics 2023, 15(1), 256; https://doi.org/10.3390/pharmaceutics15010256 - 11 Jan 2023
Cited by 4 | Viewed by 1619
Abstract
Pulmonary surfactant (PS) has been proposed as an efficient drug delivery vehicle for inhaled therapies. Its ability to adsorb and spread interfacially and transport different drugs associated with it has been studied mainly by different surface balance designs, typically interconnecting various compartments by [...] Read more.
Pulmonary surfactant (PS) has been proposed as an efficient drug delivery vehicle for inhaled therapies. Its ability to adsorb and spread interfacially and transport different drugs associated with it has been studied mainly by different surface balance designs, typically interconnecting various compartments by interfacial paper bridges, mimicking in vitro the respiratory air–liquid interface. It has been demonstrated that only a monomolecular surface layer of PS/drug is able to cross this bridge. However, surfactant films are typically organized as multi-layered structures associated with the interface. The aim of this work was to explore the contribution of surface-associated structures to the spreading of PS and the transport of drugs. We have designed a novel vehiculization balance in which donor and recipient compartments are connected by a whole three-dimensional layer of liquid and not only by an interfacial bridge. By combining different surfactant formulations and liposomes with a fluorescent lipid dye and a model hydrophobic drug, budesonide (BUD), we observed that the use of the bridge significantly reduced the transfer of lipids and drug through the air–liquid interface in comparison to what can be spread through a fully open interfacial liquid layer. We conclude that three-dimensional structures connected to the surfactant interfacial film can provide an important additional contribution to interfacial delivery, as they are able to transport significant amounts of lipids and drugs during surfactant spreading. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Figure 1

15 pages, 3004 KiB  
Article
Am80-Encapsulated Lipid Nanoparticles, Developed with the Aim of Achieving Alveolar Regeneration, Have an Improvement Effect on Pulmonary Emphysema
by Tomomi Akita, Yuki Morita, Takehiro Kawai, Kazuaki Oda, Kota Tange, Yuta Nakai and Chikamasa Yamashita
Pharmaceutics 2023, 15(1), 37; https://doi.org/10.3390/pharmaceutics15010037 - 22 Dec 2022
Cited by 1 | Viewed by 1942
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis and emphysema, and current drug treatments target its symptoms. Thus, the development of a therapeutic drug to repair alveolar destruction is urgently needed. Our previous research revealed that the synthetic retinoic acid Am80 [...] Read more.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis and emphysema, and current drug treatments target its symptoms. Thus, the development of a therapeutic drug to repair alveolar destruction is urgently needed. Our previous research revealed that the synthetic retinoic acid Am80 (1.0 mg/kg) showed a repairing effect on collapsed alveoli in a mouse model of elastase-induced emphysema. However, a further reduction in the dose is desirable to facilitate the development of a powder inhalation formulation for clinical application. We, therefore, focused on SS-OP to deliver Am80 efficiently. As a result, 0.01 mg/kg of Am80-encapsulated SS-OP nanoparticles repaired collapsed alveoli and improved the respiratory function in the mouse model of elastase induced emphysema. The results suggested that, with the use of SS-OP, the Am80 dose could be reduced. This could contribute to the development of a powder inhalation system as a curative medicine for COPD. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Graphical abstract

30 pages, 5431 KiB  
Article
Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization
by Bassant Elbardisy, Nabila Boraie and Sally Galal
Pharmaceutics 2022, 14(12), 2717; https://doi.org/10.3390/pharmaceutics14122717 - 5 Dec 2022
Cited by 4 | Viewed by 2089
Abstract
Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved [...] Read more.
Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved in nanoemulsions (NEs). However, the formulations could not resist aqueous dilution, which precluded its dilution with saline for nebulization. Thus, the current study aimed to modify the previous systems into dilutable TD-NEs and assess their suitability for a pulmonary application. In this regard, screening of various excipients was conducted to optimize the former systems; different formulations were selected and characterized in terms of physicochemical properties, nebulization performance, stability following sterilization, and biocompatibility. Results showed that the optimal system comprised of Capmul-MCM-EP:Labrafac-lipophile (1:1) (w/w) as oil, Labrasol:Poloxamer-407 (2:1) (w/w) as surfactant mixture (Smix) and water. The optimum formulation P2TD resisted aqueous dilution, exhibited reasonable drug loading (2.45 mg/mL) and globule size (25.04 nm), acceptable pH and viscosity for pulmonary administration, and could be aerosolized using a jet nebulizer. Moreover, P2TD demonstrated stability following sterilization and a favorable safety profile confirmed by both in-vitro and in-vivo toxicity studies. These favorable findings make P2TD promising for the treatment of pediatric PAH. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Graphical abstract

11 pages, 6968 KiB  
Article
Dry Powder Formulation of Simvastatin Nanoparticles for Potential Application in Pulmonary Arterial Hypertension
by Shalaleh Zendehdel Baher, Shadi Yaqoubi, Kofi Asare-Addo, Hamed Hamishehkar and Ali Nokhodchi
Pharmaceutics 2022, 14(5), 895; https://doi.org/10.3390/pharmaceutics14050895 - 20 Apr 2022
Cited by 15 | Viewed by 3769
Abstract
It has been hypothesized that simvastatin could be used to treat pulmonary arterial hypertension (PAH). This study is intended to formulate a simvastatin nanoparticle dry powder inhalation (DPI) formulation. Simvastatin nanoparticles were prepared via an emulsification and homogenization-extrusion method, followed by spray drying [...] Read more.
It has been hypothesized that simvastatin could be used to treat pulmonary arterial hypertension (PAH). This study is intended to formulate a simvastatin nanoparticle dry powder inhalation (DPI) formulation. Simvastatin nanoparticles were prepared via an emulsification and homogenization-extrusion method, followed by spray drying of the colloidal suspension of simvastatin nanoparticles containing mannitol to get it into a respirable size. Particle size distribution, morphology, and crystallinity of the fabricated nanoparticles of the obtained microparticles for DPI formulation were assessed by dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray diffraction pattern (XRPD), respectively. Aerosolization performance of the DPI formulation was assessed by the Next Generation Impactor (NGI) equipped with an Aerolizer®. Simvastatin nanoparticles were around 100 nm with a very narrow size distribution (PDI = 0.105). The X-ray diffraction pattern revealed that the crystallinity of simvastatin was decreased by the spray drying procedure. Microscopic images displayed that gathered nanoparticles were in the suitable inhalable range and had the appropriate shape and surface properties for pulmonary delivery. Aerosolization assessment by the NGI indicated a suitable inhalation performance (fine particle fraction of 20%). In conclusion, the results confirmed that the spray drying technique for simvastatin can be optimized to obtain simvastatin aggregated nanoparticles without any coarse carrier to be used in DPI formulation for better deposition of the drug in the lungs for local treatment of PAH. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Graphical abstract

11 pages, 8901 KiB  
Article
Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291
by Alan B. Dogan, Nathan A. Rohner, Julianne N. P. Smith, Jessica A. Kilgore, Noelle S. Williams, Sanford D. Markowitz, Horst A. von Recum and Amar B. Desai
Pharmaceutics 2022, 14(1), 85; https://doi.org/10.3390/pharmaceutics14010085 - 30 Dec 2021
Viewed by 1993
Abstract
As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Although bolus parenteral administrations have [...] Read more.
As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Although bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady-state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles—specifically, β-CD microparticles (β-CD MPs)—to extend the delivery of the 15-PGDH inhibitor, (+)SW033291, to over one week. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Graphical abstract

Review

Jump to: Research

29 pages, 2212 KiB  
Review
Therapeutic Potential of Controlled Delivery Systems in Asthma: Preclinical Development of Flavonoid-Based Treatments
by Sergio M. Borghi, Tiago H. Zaninelli, Jéssica B. Carra, Olivia K. Heintz, Marcela M. Baracat, Sandra R. Georgetti, Fabiana T. M. C. Vicentini, Waldiceu A. Verri and Rubia Casagrande
Pharmaceutics 2023, 15(1), 1; https://doi.org/10.3390/pharmaceutics15010001 - 20 Dec 2022
Cited by 4 | Viewed by 1829
Abstract
Asthma is a chronic disease with increasing prevalence and incidence, manifested by allergic inflammatory reactions, and is life-threatening for patients with severe disease. Repetitive challenges with the allergens and limitation of treatment efficacy greatly dampens successful management of asthma. The adverse events related [...] Read more.
Asthma is a chronic disease with increasing prevalence and incidence, manifested by allergic inflammatory reactions, and is life-threatening for patients with severe disease. Repetitive challenges with the allergens and limitation of treatment efficacy greatly dampens successful management of asthma. The adverse events related to several drugs currently used, such as corticosteroids and β-agonists, and the low rigorous adherence to preconized protocols likely compromises a more assertive therapy. Flavonoids represent a class of natural compounds with extraordinary antioxidant and anti-inflammatory properties, with their potential benefits already demonstrated for several diseases, including asthma. Advanced technology has been used in the pharmaceutical field to improve the efficacy and safety of drugs. Notably, there is also an increasing interest for the application of these techniques using natural products as active molecules. Flavones, flavonols, flavanones, and chalcones are examples of flavonoid compounds that were tested in controlled delivery systems for asthma treatment, and which achieved better treatment results in comparison to their free forms. This review aims to provide a comprehensive understanding of the development of novel controlled delivery systems to enhance the therapeutic potential of flavonoids as active molecules for asthma treatment. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Figure 1

25 pages, 1466 KiB  
Review
Could the Lung Be a Gateway for Amphotericin B to Attack the Army of Fungi?
by Beatriz Ferreira de Carvalho Patricio, Juliana Oliveira da Silva Lopes Pereira, Michelle Alvares Sarcinelli, Bianca Portugal Tavares de Moraes, Helvécio Vinicius Antunes Rocha and Cassiano Felippe Gonçalves-de-Albuquerque
Pharmaceutics 2022, 14(12), 2707; https://doi.org/10.3390/pharmaceutics14122707 - 3 Dec 2022
Cited by 1 | Viewed by 2725
Abstract
Fungal diseases are a significant cause of morbidity and mortality worldwide, primarily affecting immunocompromised patients. Aspergillus, Pneumocystis, and Cryptococcus are opportunistic fungi and may cause severe lung disease. They can develop mechanisms to evade the host immune system and colonize or [...] Read more.
Fungal diseases are a significant cause of morbidity and mortality worldwide, primarily affecting immunocompromised patients. Aspergillus, Pneumocystis, and Cryptococcus are opportunistic fungi and may cause severe lung disease. They can develop mechanisms to evade the host immune system and colonize or cause lung disease. Current fungal infection treatments constitute a few classes of antifungal drugs with significant fungi resistance development. Amphotericin B (AmB) has a broad-spectrum antifungal effect with a low incidence of resistance. However, AmB is a highly lipophilic antifungal with low solubility and permeability and is unstable in light, heat, and oxygen. Due to the difficulty of achieving adequate concentrations of AmB in the lung by intravenous administration and seeking to minimize adverse effects, nebulized AmB has been used. The pulmonary pathway has advantages such as its rapid onset of action, low metabolic activity at the site of action, ability to avoid first-pass hepatic metabolism, lower risk of adverse effects, and thin thickness of the alveolar epithelium. This paper presented different strategies for pulmonary AmB delivery, detailing the potential of nanoformulation and hoping to foster research in the field. Our finds indicate that despite an optimistic scenario for the pulmonary formulation of AmB based on the encouraging results discussed here, there is still no product registration on the FDA nor any clinical trial undergoing ClinicalTrial.gov. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Figure 1

26 pages, 2865 KiB  
Review
Packaging and Delivery of Asthma Therapeutics
by Bryan J. Mathis, Misa Kusumoto, Alexander Zaboronok and Yuji Hiramatsu
Pharmaceutics 2022, 14(1), 92; https://doi.org/10.3390/pharmaceutics14010092 - 31 Dec 2021
Cited by 5 | Viewed by 3386
Abstract
Asthma is a life-altering, chronic disease of heterogenous origin that features a complex interplay of immune and environmental signaling. Although very little progress has been made in prevention, diverse types of medications and delivery systems, including nanoscale systems, have been or are currently [...] Read more.
Asthma is a life-altering, chronic disease of heterogenous origin that features a complex interplay of immune and environmental signaling. Although very little progress has been made in prevention, diverse types of medications and delivery systems, including nanoscale systems, have been or are currently being developed to control airway inflammation and prevent exacerbations and fibrosis. These medications are delivered through mechanical methods, with various inhalers (with benefits and drawbacks) existing, and new types offering some variety in delivery. Of particular interest is the progress being made in nanosized materials for efficient penetration into the epithelial mucus layer and delivery into the deepest parts of the lungs. Liposomes, nanoparticles, and extracellular vesicles, both natural and synthetic, have been explored in animal models of asthma and have produced promising results. This review will summarize and synthesize the latest developments in both macro-(inhaler) and micro-sized delivery systems for the purpose of treating asthma patients. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Asthma and Pulmonary Diseases)
Show Figures

Graphical abstract

Back to TopTop