---
title: "Ciclesonide–Indacaterol Liposomes: Optimizing ICS/LABA Pulmonary Delivery for Asthma"
id: "pubmed-42486206"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42486206"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42486206/"
doi: "10.1016/j.ijpharm.2026.127217"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Ciclesonide–Indacaterol Liposomes: Optimizing ICS/LABA Pulmonary Delivery for Asthma
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42486206
- **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/42486206/)
- **DOI:** [10.1016/j.ijpharm.2026.127217](https://doi.org/10.1016%2Fj.ijpharm.2026.127217)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Combination inhaled corticosteroid–long-acting β2-agonist therapy is central to asthma care, but lung delivery is limited by **drug hydrophobicity**, mucus entrapment and macrophage clearance, which reduce target-site availability and force higher doses or more frequent administration. - The authors report systematic optimization of a **liposomal** co-delivery system for **ciclesonide (CIC)** and **indacaterol maleate (IND)** to overcome pulmonary barriers and improve efficacy. - Among PEGylated lipids tested, **DSPE-PEG** was selected because its amine function enhances IND encapsulation through amine–phosphate interactions and its 18-carbon chain showed better macrophage biocompatibility than C14 and C16 analogs. - A DSPE-PEG content of **15%** was used to balance mucopenetration and macrophage evasion, and this formulation improved the ex vivo relaxation effect of IND compared with the free drug solution. - **DLPC** was chosen as the main phospholipid because its double unsaturation (two double bonds) was required to achieve high encapsulation efficiency for both hydrophobic drugs, facilitate epithelial cell uptake in vitro, and enhance ex vivo potency of IND. - In an ovalbumin (OVA)-induced murine asthma model, the optimized liposomal formulation significantly attenuated **airway hyperresponsiveness** and suppressed the type 2 inflammatory cascade, including epithelial alarmins, downstream cytokines, and inflammatory cell recruitment. - Liposomal encapsulation provided a potential **dose-sparing** effect for both CIC and IND, indicating more efficient pulmonary delivery and a promising strategy for asthma and possibly other respiratory diseases. - The study emphasizes formulation-driven solutions (lipid choice and PEGylation level) to biological barriers rather than altering active agents; detailed quantitative metrics and some experimental parameters were reported in the original article but are not reproduced in full here.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 22. # Ciclesonide/indacaterol-encapsulated liposomes: optimizing corticosteroid-bronchodilator therapy for a more effective approach to asthma management [Tuan Nghia Dinh](https://pubmed.ncbi.nlm.nih.gov/?term=Dinh+TN&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Benedetta Bottero](https://pubmed.ncbi.nlm.nih.gov/?term=Bottero+B&cauthor_id=42486206)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-2 "Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Fabienne Perin](https://pubmed.ncbi.nlm.nih.gov/?term=Perin+F&cauthor_id=42486206)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-2 "Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Laure-Anne Bya](https://pubmed.ncbi.nlm.nih.gov/?term=Bya+LA&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Anna Lechanteur](https://pubmed.ncbi.nlm.nih.gov/?term=Lechanteur+A&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Brigitte Evrard](https://pubmed.ncbi.nlm.nih.gov/?term=Evrard+B&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Géraldine Piel](https://pubmed.ncbi.nlm.nih.gov/?term=Piel+G&cauthor_id=42486206)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-3 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: geraldine.piel@uliege.be."), [Didier Cataldo](https://pubmed.ncbi.nlm.nih.gov/?term=Cataldo+D&cauthor_id=42486206)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#full-view-affiliation-4 "Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: Didier.Cataldo@uliege.be.") Affiliations Expand ### Affiliations * 1 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium. * 2 Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium. * 3 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: geraldine.piel@uliege.be. * 4 Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: Didier.Cataldo@uliege.be. * PMID: **42486206** * DOI: [ 10.1016/j.ijpharm.2026.127217 ](https://doi.org/10.1016/j.ijpharm.2026.127217) Item in Clipboard # Ciclesonide/indacaterol-encapsulated liposomes: optimizing corticosteroid-bronchodilator therapy for a more effective approach to asthma management Tuan Nghia Dinh et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42486206/) . 2026 Sep 5:702:127217. doi: 10.1016/j.ijpharm.2026.127217. Epub 2026 Jul 22. ### Authors [Tuan Nghia Dinh](https://pubmed.ncbi.nlm.nih.gov/?term=Dinh+TN&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Benedetta Bottero](https://pubmed.ncbi.nlm.nih.gov/?term=Bottero+B&cauthor_id=42486206)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-2 "Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Fabienne Perin](https://pubmed.ncbi.nlm.nih.gov/?term=Perin+F&cauthor_id=42486206)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-2 "Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Laure-Anne Bya](https://pubmed.ncbi.nlm.nih.gov/?term=Bya+LA&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Anna Lechanteur](https://pubmed.ncbi.nlm.nih.gov/?term=Lechanteur+A&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Brigitte Evrard](https://pubmed.ncbi.nlm.nih.gov/?term=Evrard+B&cauthor_id=42486206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium."), [Géraldine Piel](https://pubmed.ncbi.nlm.nih.gov/?term=Piel+G&cauthor_id=42486206)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-3 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines \(CIRM\), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: geraldine.piel@uliege.be."), [Didier Cataldo](https://pubmed.ncbi.nlm.nih.gov/?term=Cataldo+D&cauthor_id=42486206)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42486206/#short-view-affiliation-4 "Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: Didier.Cataldo@uliege.be.") ### Affiliations * 1 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium. * 2 Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium. * 3 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: geraldine.piel@uliege.be. * 4 Laboratory of Tumor and Development Biology, GIGA-Cancer and CHU of Liège, University of Liège, Avenue Hippocrate 15, 4000 Liege, Belgium. Electronic address: Didier.Cataldo@uliege.be. * PMID: **42486206** * DOI: [ 10.1016/j.ijpharm.2026.127217 ](https://doi.org/10.1016/j.ijpharm.2026.127217) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Combination therapy with inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA) is the clinical cornerstone of asthma management. However, therapeutic efficacy is frequently compromised by high drug hydrophobicity, which enhances entrapment within the pulmonary mucus and promotes recognition and clearance from alveolar macrophages. This results in reduced drug availability at the target site, requiring higher doses or more frequent administrations. To overcome these biological barriers and improve the therapeutic outcomes, we report the systematic optimization of a liposomal formulation for the co-delivery of ciclesonide (CIC) and indacaterol maleate (IND). Among various PEGylated lipids, DSPE-PEG was chosen because its amine function maximizes IND encapsulation via amine-phosphate interactions and its 18-carbon chain exhibited superior biocompatibility with macrophages compared to C14 and C16 analogs. Incorporating DSPE-PEG at 15% ensured robust mucopenetration and macrophage evasion, significantly improving the ex vivo relaxation effect of IND compared to the drug solution. DLPC was utilized as the main phospholipid since its high degree of unsaturation (two double bonds) was essential for achieving high encapsulation efficiency of both hydrophobic payloads, efficient epithelial cell uptake in vitro and improved ex vivo efficacy and potency of IND. In an OVA-induced murine model, the optimized formulation markedly attenuated airway hyperresponsiveness and suppressed the type 2 inflammatory cascade, including upstream epithelial-derived alarmins, downstream inflammatory cytokines and inflammatory cell recruitment. Notably, liposomal encapsulation also provided a potential dose-sparing effect for both compounds, suggesting that efficient pulmonary delivery of ICS/LABA via lipid nanoparticles is a promising asthma management strategy and may be applicable to other respiratory diseases. **Keywords:** Asthma; Ciclesonide; Indacaterol maleate; Lipid; Liposome; Pulmonary delivery. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ [Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)]. ](https://pubmed.ncbi.nlm.nih.gov/38309959/) Pulmonary Function and Clinical Respiratory Physiology Committee of Chinese Association of Chest Physicians; Chinese Thoracic Society; Pulmonary Function Group of Respiratory Branch of Chinese Geriatric Society.Pulmonary Function and Clinical Respiratory Physiology Committee of Chinese Association of Chest Physicians, et al.Zhonghua Jie He He Hu Xi Za Zhi. 2024 Feb 12;47(2):101-119. doi: 10.3760/cma.j.cn112147-20231019-00247.Zhonghua Jie He He Hu Xi Za Zhi. 2024.PMID: 38309959Chinese. * [ Once-daily, single-inhaler mometasone-indacaterol-glycopyrronium versus mometasone-indacaterol or twice-daily fluticasone-salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study. ](https://pubmed.ncbi.nlm.nih.gov/32653074/) Kerstjens HAM, Maspero J, Chapman KR, van Zyl-Smit RN, Hosoe M, Tanase AM, Lavecchia C, Pethe A, Shu X, D'Andrea P; IRIDIUM trial investigators.Kerstjens HAM, et al.Lancet Respir Med. 2020 Oct;8(10):1000-1012. doi: 10.1016/S2213-2600(20)30190-9. Epub 2020 Jul 9.Lancet Respir Med. 2020.PMID: 32653074Clinical Trial. * [ Once-daily mometasone plus indacaterol versus mometasone or twice-daily fluticasone plus salmeterol in patients with inadequately controlled asthma (PALLADIUM): a randomised, double-blind, triple-dummy, controlled phase 3 study. ](https://pubmed.ncbi.nlm.nih.gov/32653075/) van Zyl-Smit RN, Krüll M, Gessner C, Gon Y, Noga O, Richard A, de Los Reyes A, Shu X, Pethe A, Tanase AM, D'Andrea P; PALLADIUM trial investigators.van Zyl-Smit RN, et al.Lancet Respir Med. 2020 Oct;8(10):987-999. doi: 10.1016/S2213-2600(20)30178-8. Epub 2020 Jul 9.Lancet Respir Med. 2020.PMID: 32653075Clinical Trial. * [ [Guidelines for the prevention and management of bronchial asthma (2024 edition)]. ](https://pubmed.ncbi.nlm.nih.gov/40050074/) Chinese Thoracic Society, Chinese Medical Association.Chinese Thoracic Society, Chinese Medical Association.Zhonghua Jie He He Hu Xi Za Zhi. 2025 Mar 12;48(3):208-248. doi: 10.3760/cma.j.cn112147-20241013-00601.Zhonghua Jie He He Hu Xi Za Zhi. 2025.PMID: 40050074Chinese. * [ A Review of the Unique Drug Development Strategy of Indacaterol Acetate/Glycopyrronium Bromide/Mometasone Furoate: A First-in-Class, Once-Daily, Single-Inhaler, Fixed-Dose Combination Treatment for Asthma. ](https://pubmed.ncbi.nlm.nih.gov/35072888/) Brittain D, D'Andrea P, Gruen E, Hosoe M, Jain D, Jauernig J, Pethe A, Scosyrev E, Tanase AM, Tillmann HC.Brittain D, et al.Adv Ther. 2022 Jun;39(6):2365-2378. doi: 10.1007/s12325-021-02025-w. Epub 2022 Jan 24.Adv Ther. 2022.PMID: 35072888Free PMC article.Review. 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