---
title: "Advanced Pulmonary Drug Delivery Systems: Key Mechanisms, Carriers, Devices, and Clinical Applicat"
id: "pubmed-42789236"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42789236"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42789236/"
doi: "10.1007/s41030-026-00387-6"
published_at: "2026-09-25T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Advanced Pulmonary Drug Delivery Systems: Key Mechanisms, Carriers, Devices, and Clinical Applicat
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42789236
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42789236/)
- **DOI:** [10.1007/s41030-026-00387-6](https://doi.org/10.1007%2Fs41030-026-00387-6)
- **Published At:** 2026-09-25T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Pulmonary drug delivery enables targeted, noninvasive administration to the lungs for both respiratory and systemic diseases, offering **rapid onset of action**, lower required doses, and reduced systemic adverse effects. - The field faces persistent challenges including formulation stability, aerosol performance, lung clearance mechanisms, and regulatory approval pathways that limit translation. - Anatomical, physiological, pharmaceutical, and device-related factors influence **aerosol deposition** and therapeutic performance in the lungs. - Principal particle deposition mechanisms include **inertial impaction**, gravitational sedimentation, **Brownian diffusion**, interception, and electrostatic interactions; understanding these is central to optimizing delivery. - Advanced pulmonary drug carrier systems discussed include **liposomes**, **nanoparticles**, large porous particles, **dendrimers**, polymeric micelles, biodegradable polymers, and lactose-based dry powder platforms; these carriers aim to improve drug stability, controlled release, lung retention, and site-specific targeting. - Particle engineering technologies and inhalation devices are evolving; common and advanced devices covered include pressurized metered-dose inhalers, **dry powder inhalers**, nebulizers, soft mist inhalers, and **smart inhaler** platforms. - Clinical indications extend beyond asthma and COPD to cystic fibrosis, pulmonary infections, and pulmonary arterial hypertension; investigational and emerging applications include tuberculosis, diabetes, vaccination, gene therapy, and cancer. - Future directions highlighted are personalized pulmonary medicine, inhaled biologics and **mRNA therapeutics**, environmentally sustainable inhaler technologies, artificial intelligence-assisted formulation and device optimization, and evolving regulatory frameworks. - Continued advancements will aim to improve drug targeting, optimize therapeutic performance, and broaden pulmonary delivery applications in clinical practice.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # Advanced Pulmonary Drug Delivery Systems: A Narrative Review [Dil Afrose](https://pubmed.ncbi.nlm.nih.gov/?term=Afrose+D&cauthor_id=42789236)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-1 "Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark."), [Melika Valizadeh](https://pubmed.ncbi.nlm.nih.gov/?term=Valizadeh+M&cauthor_id=42789236)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-2 "Pulmonary Rehabilitation Research Center \(PRRC\), National Research Institute of Tuberculosis and Lung Diseases \(NRITLD\), Shahid Beheshti University of Medical Sciences, Tehran, Iran."), [Shailesh B Kolekar](https://pubmed.ncbi.nlm.nih.gov/?term=Kolekar+SB&cauthor_id=42789236)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-3 "Department of Medicine, Helsingborg Hospital, Lund University, Region Skane, Sweden."), [Mano J Mathew](https://pubmed.ncbi.nlm.nih.gov/?term=Mathew+MJ&cauthor_id=42789236)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-4 "EFREI Paris EFREI Research Lab, Panthéon-Assas University, 30-32 Avenue de La République, 94800, Villejuif, France."), [Alexandr Ceasovschih](https://pubmed.ncbi.nlm.nih.gov/?term=Ceasovschih+A&cauthor_id=42789236)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-5 "Grigore T. Popa University of Medicine and Pharmacy, 700115, Iasi, Romania."), [Alexandru Corlateanu](https://pubmed.ncbi.nlm.nih.gov/?term=Corlateanu+A&cauthor_id=42789236)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-6 "Department of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", 2004, Chisinau, Moldova."), [Pradeesh Sivapalan](https://pubmed.ncbi.nlm.nih.gov/?term=Sivapalan+P&cauthor_id=42789236)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-7 "Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark. pradeesh.sivapalan.02@regionh.dk.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#full-view-affiliation-8 "Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. pradeesh.sivapalan.02@regionh.dk.") Affiliations Expand ### Affiliations * 1 Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark. * 2 Pulmonary Rehabilitation Research Center (PRRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. * 3 Department of Medicine, Helsingborg Hospital, Lund University, Region Skane, Sweden. * 4 EFREI Paris EFREI Research Lab, Panthéon-Assas University, 30-32 Avenue de La République, 94800, Villejuif, France. * 5 Grigore T. Popa University of Medicine and Pharmacy, 700115, Iasi, Romania. * 6 Department of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", 2004, Chisinau, Moldova. * 7 Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark. pradeesh.sivapalan.02@regionh.dk. * 8 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. pradeesh.sivapalan.02@regionh.dk. * PMID: **42789236** * DOI: [ 10.1007/s41030-026-00387-6 ](https://doi.org/10.1007/s41030-026-00387-6) Item in Clipboard # Advanced Pulmonary Drug Delivery Systems: A Narrative Review Dil Afrose et al. Pulm Ther. 2026. Show details Display options Display options Format Abstract PubMed PMID Pulm Ther Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Pulm+Ther%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Pulm+Ther%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42789236/) . 2026 Sep 25. doi: 10.1007/s41030-026-00387-6. Online ahead of print. ### Authors [Dil Afrose](https://pubmed.ncbi.nlm.nih.gov/?term=Afrose+D&cauthor_id=42789236)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-1 "Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark."), [Melika Valizadeh](https://pubmed.ncbi.nlm.nih.gov/?term=Valizadeh+M&cauthor_id=42789236)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-2 "Pulmonary Rehabilitation Research Center \(PRRC\), National Research Institute of Tuberculosis and Lung Diseases \(NRITLD\), Shahid Beheshti University of Medical Sciences, Tehran, Iran."), [Shailesh B Kolekar](https://pubmed.ncbi.nlm.nih.gov/?term=Kolekar+SB&cauthor_id=42789236)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-3 "Department of Medicine, Helsingborg Hospital, Lund University, Region Skane, Sweden."), [Mano J Mathew](https://pubmed.ncbi.nlm.nih.gov/?term=Mathew+MJ&cauthor_id=42789236)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-4 "EFREI Paris EFREI Research Lab, Panthéon-Assas University, 30-32 Avenue de La République, 94800, Villejuif, France."), [Alexandr Ceasovschih](https://pubmed.ncbi.nlm.nih.gov/?term=Ceasovschih+A&cauthor_id=42789236)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-5 "Grigore T. Popa University of Medicine and Pharmacy, 700115, Iasi, Romania."), [Alexandru Corlateanu](https://pubmed.ncbi.nlm.nih.gov/?term=Corlateanu+A&cauthor_id=42789236)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-6 "Department of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", 2004, Chisinau, Moldova."), [Pradeesh Sivapalan](https://pubmed.ncbi.nlm.nih.gov/?term=Sivapalan+P&cauthor_id=42789236)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-7 "Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark. pradeesh.sivapalan.02@regionh.dk.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42789236/#short-view-affiliation-8 "Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. pradeesh.sivapalan.02@regionh.dk.") ### Affiliations * 1 Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark. * 2 Pulmonary Rehabilitation Research Center (PRRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. * 3 Department of Medicine, Helsingborg Hospital, Lund University, Region Skane, Sweden. * 4 EFREI Paris EFREI Research Lab, Panthéon-Assas University, 30-32 Avenue de La République, 94800, Villejuif, France. * 5 Grigore T. Popa University of Medicine and Pharmacy, 700115, Iasi, Romania. * 6 Department of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", 2004, Chisinau, Moldova. * 7 Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital- Herlev and Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark. pradeesh.sivapalan.02@regionh.dk. * 8 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. pradeesh.sivapalan.02@regionh.dk. * PMID: **42789236** * DOI: [ 10.1007/s41030-026-00387-6 ](https://doi.org/10.1007/s41030-026-00387-6) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Pulmonary drug delivery systems have gained increasing attention as an effective strategy for the treatment of both respiratory and systemic diseases by enabling targeted, noninvasive, and efficient drug administration through the lungs, with advantages including rapid onset of action, lower drug doses, and reduced systemic adverse effects. Despite these advances, challenges related to formulation stability, aerosol performance, lung clearance mechanisms, and regulatory approval remain. This review explores advanced pulmonary drug delivery systems, with emphasis on the anatomical, physiological, pharmaceutical, and device-related factors that influence aerosol deposition and therapeutic performance. The review examines key mechanisms of particle deposition such as inertial impaction, gravitational sedimentation, Brownian diffusion, interception, and electrostatic interactions, and advanced pulmonary drug carrier systems, including liposomes, nanoparticles, large porous particles, dendrimers, polymeric micelles, biodegradable polymers, and lactose-based dry powder platforms, which enhance drug stability, controlled release, lung retention, and site-specific targeting. The review further summarizes advances in particle engineering technologies and common and advanced inhalation devices, including pressurized metered-dose inhalers, dry powder inhalers, nebulizers, soft mist inhalers, and smart inhaler platforms. Clinical applications of pulmonary drug delivery extend beyond asthma and chronic obstructive pulmonary disease (COPD) to include cystic fibrosis, pulmonary infections, and pulmonary arterial hypertension, while emerging applications in tuberculosis, diabetes, vaccination, gene therapy, and cancer continue to be investigated. Future directions include personalized pulmonary medicine, inhaled biologics and mRNA therapeutics, environmentally sustainable inhaler technologies, artificial intelligence-assisted formulation and device optimization, and evolving regulatory frameworks. Advancements in pulmonary drug delivery technologies may focus on improving drug targeting, optimizing therapeutic performance, and broadening their application in modern clinical practice. **Keywords:** Inhalation devices; Nanoparticles; Nebulizer; Particle engineering; Particle technology; Pressurized metered-dose inhalers; Pulmonary drug delivery. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Conflict of Interest: Dil Afrose, Melika Valizadeh, Shailesh B. Kolekar, Mano J. Mathew, Alexandr Ceasovschih, Alexandru Corlateanu and Pradeesh Sivapalan have nothing to disclose. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. ## References 1. 1. Department of Data and Analytics (DNA) Analytics and Delivery for Impact (DDI) WHO Geneva D of D WHO methods and data sources for country-level causes of death 2000–2021. 55. 2. 1. Govender M, Choonara YE. Drug delivery systems for respiratory diseases: insights into the therapeutic innovations for pulmonary administration. Pharmaceutics (Basel). 2025;17:539. - [DOI](https://doi.org/10.3390/pharmaceutics17050539) 3. 1. Subramani PK, Remya PN, Narayanasamy D. The role of pulmonary drug delivery in modern therapeutics: an overview. Cureus. 2024;16:e68639. . - [DOI](https://doi.org/10.7759/cureus.68639) 4. 1. Okauchi S, Kinoshita K, Sato S, et al. Rinsing of oropharynx and storage place of respiratory medicine inhaler: a cross-sectional audit. J Gen Fam Med. 2019;20:101–6. . - [DOI](https://doi.org/10.1002/jgf2.241) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/31065474/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/6498108/) 5. 1. Maccari JG, Teixeira C, Gazzana MB, et al. Inhalation therapy in mechanical ventilation. J Bras Pneumol. 2015;41:467–72. . - [DOI](https://doi.org/10.1590/s1806-37132015000000035) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26578139/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4635094/) Show all 81 references ## Publication types * Systematic Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Systematic+Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Systematic+Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42789236/) [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM **Send To** * [Clipboard](https://pubmed.ncbi.nlm.nih.gov/42789236/) * [Email](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42789236%2F%23open-email-panel) * [Save](https://pubmed.ncbi.nlm.nih.gov/42789236/) * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42789236%2F%23open-bibliography-panel) * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42789236%2F%23open-collections-panel) * [Citation Manager](https://pubmed.ncbi.nlm.nih.gov/42789236/) [x] NCBI Literature Resources [MeSH](https://www.ncbi.nlm.nih.gov/mesh/) [PMC](https://www.ncbi.nlm.nih.gov/pmc/) [Bookshelf](https://www.ncbi.nlm.nih.gov/books) [Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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