Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections

<b>Background/Objectives:</b> Respiratory bacterial infections remain a significant global health challenge, with effective drug delivery to the lungs being crucial for successful treatment. This study aimed to develop a lactose-free dry powder inhaler (DPI) formulation containing azithr...

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Main Authors: Gracia Molina, Dolores R. Serrano, María Auxiliadora Dea-Ayuela, Carmina Rodriguez, Elena González-Burgos, Brayan J. Anaya
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/17/6/770
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author Gracia Molina
Dolores R. Serrano
María Auxiliadora Dea-Ayuela
Carmina Rodriguez
Elena González-Burgos
Brayan J. Anaya
author_facet Gracia Molina
Dolores R. Serrano
María Auxiliadora Dea-Ayuela
Carmina Rodriguez
Elena González-Burgos
Brayan J. Anaya
author_sort Gracia Molina
collection DOAJ
description <b>Background/Objectives:</b> Respiratory bacterial infections remain a significant global health challenge, with effective drug delivery to the lungs being crucial for successful treatment. This study aimed to develop a lactose-free dry powder inhaler (DPI) formulation containing azithromycin (AZM) microparticles for enhanced pulmonary delivery. <b>Methods:</b> Using a quality-by-design approach, an optimized formulation (4% AZM, 20% leucine, and 76% mannitol) was achieved. <b>Results:</b> The formulation demonstrated excellent aerodynamic properties with a mass median aerodynamic diameter (MMAD) of 2.72 μm ± 0.01 μm and fine particle fraction (FPF) (<5 μm) of 65.42% ± 5.12%. AZM-loaded microparticles exhibited enhanced efficacy against <i>Pseudomonas aeruginosa</i> with a two-fold reduction in the minimum bactericidal concentration (7.81 μg/mL vs. 15.62 μg/mL) compared to unprocessed AZM, while maintaining activity against <i>Streptococcus pneumoniae</i>. AZM microparticles demonstrated good biocompatibility with red blood cells and bronchial epithelial cells at therapeutic concentrations. <b>Conclusions:</b> These findings establish a promising lactose-free antibiotic formulation for targeted pulmonary delivery with enhanced antimicrobial efficacy.
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spelling doaj-art-a057266d46ff42758bb4e7241b312c9d2025-08-20T03:16:25ZengMDPI AGPharmaceutics1999-49232025-06-0117677010.3390/pharmaceutics17060770Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial InfectionsGracia Molina0Dolores R. Serrano1María Auxiliadora Dea-Ayuela2Carmina Rodriguez3Elena González-Burgos4Brayan J. Anaya5Pharmaceutics and Food Technology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, SpainPharmaceutics and Food Technology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, SpainDepartment of Pharmacy, Universidad Cardenal Herrera-CEU, CEU University, 46115 Valencia, SpainDepartment of Microbiology and Parasitology, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), 28040 Madrid, SpainDepartment of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), 28040 Madrid, SpainPharmaceutics and Food Technology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain<b>Background/Objectives:</b> Respiratory bacterial infections remain a significant global health challenge, with effective drug delivery to the lungs being crucial for successful treatment. This study aimed to develop a lactose-free dry powder inhaler (DPI) formulation containing azithromycin (AZM) microparticles for enhanced pulmonary delivery. <b>Methods:</b> Using a quality-by-design approach, an optimized formulation (4% AZM, 20% leucine, and 76% mannitol) was achieved. <b>Results:</b> The formulation demonstrated excellent aerodynamic properties with a mass median aerodynamic diameter (MMAD) of 2.72 μm ± 0.01 μm and fine particle fraction (FPF) (<5 μm) of 65.42% ± 5.12%. AZM-loaded microparticles exhibited enhanced efficacy against <i>Pseudomonas aeruginosa</i> with a two-fold reduction in the minimum bactericidal concentration (7.81 μg/mL vs. 15.62 μg/mL) compared to unprocessed AZM, while maintaining activity against <i>Streptococcus pneumoniae</i>. AZM microparticles demonstrated good biocompatibility with red blood cells and bronchial epithelial cells at therapeutic concentrations. <b>Conclusions:</b> These findings establish a promising lactose-free antibiotic formulation for targeted pulmonary delivery with enhanced antimicrobial efficacy.https://www.mdpi.com/1999-4923/17/6/770azithromycindry powder inhalerlactose-freemicroparticlespulmonary drug delivery
spellingShingle Gracia Molina
Dolores R. Serrano
María Auxiliadora Dea-Ayuela
Carmina Rodriguez
Elena González-Burgos
Brayan J. Anaya
Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections
Pharmaceutics
azithromycin
dry powder inhaler
lactose-free
microparticles
pulmonary drug delivery
title Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections
title_full Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections
title_fullStr Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections
title_full_unstemmed Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections
title_short Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections
title_sort lung delivery of lactose free microparticles loaded with azithromycin for the treatment of bacterial infections
topic azithromycin
dry powder inhaler
lactose-free
microparticles
pulmonary drug delivery
url https://www.mdpi.com/1999-4923/17/6/770
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