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Cited by 5Inhalation and Respiratory Drug DeliveryAdvanced Drug Delivery SystemsNanoparticle-Based Drug Delivery

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Lung-Targeted Itraconazole Delivery Using PVA-Based Nano-in-Microparticles for Improved Treatment of Pulmonary Aspergillosis

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Jeong, Jin-Hyuk, Lee, Hee-Sung, Choi, Jae-Cheol, Kang, Ji-Hyun, Kim, Dong-Wook, Park, Chan-Su, Park, Chun-Woong·2025·International Journal of Nanomedicine
DOI 10.2147/ijn.s511099PMC PMC11994481
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Abstract

Purpose: Pulmonary aspergillosis (PA) presents a substantial therapeutic challenge, especially in immunocompromised patients, where conventional systemic treatments like oral and intravenous routes often result in limited efficacy and increased adverse effects. This study focuses on the development and evaluation of an inhalable itraconazole (ITZ) formulation within a nanoparticles-in-microparticles (NIM) system. Methods: Polyvinyl alcohol 500 (PVA), used in varying concentrations, played a crucial role as a stabilizer in both the wet bead milling and spray drying processes, enhancing drug release and aerodynamic performance. The influence of PVA ratios on drug penetration into pulmonary mucus and interactions with pulmonary defense mechanisms were thoroughly investigated through in-vitro simulations. Results: Pharmacokinetic analysis in Sprague-Dawley (SD) rats revealed enhanced distribution of ITZ-NIMs in pulmonary tissues and bronchoalveolar lavage fluid (BALF), representing a significant improvement in localized drug concentration. Efficacy against Aspergillus fumigatus was confirmed by a reduction in galactomannan levels, inhibition of fungal growth in lung tissues, and increased survival rates. Importantly, pulmonary delivery of ITZ significantly reduced hepatotoxicity markers, including alanine aminotransferase (ALT) and alkaline phosphatase (ALP), when compared to oral administration. Conclusion: The incorporation of PVA in NIM technology demonstrated not only improved pulmonary targeting and drug release but also minimized systemic toxicity, highlighting the potential of nanoparticle-based inhalation systems in treating respiratory fungal infections like aspergillosis. These findings emphasize the pivotal role of PVA in the formulation, stability, and therapeutic efficacy of NIM-based drug delivery systems for pulmonary applications, advancing the use of nanoparticle technology in respiratory drug delivery. Keywords: Polyvinyl alcohol 500, PVA, dry powder inhaler, DPI, nanoparticles-in-microparticles, NIM, itraconazole, ITZ, aspergillosis

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Metadata

Authors
Jeong, J.-H., Lee, H.-S., Choi, J.-C., Kang, J.-H., Kim, D.-W., Park, C.-S., & Park, C.-W.
Affiliations
  • Chungbuk National University (KR)
  • Jeonbuk National University (KR)
  • Wonkwang University (KR)
Corresponding author
  • Park, Chan-Su
  • Park, Chun-Woong
ORCID
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2025-04
Volume
Volume 20
Pages
4357-4380
ISSN
  • 1176-9114 (ISSN-L)
  • 1178-2013
DOI
10.2147/ijn.s511099
PMC
PMC11994481
OpenAlex
W4409269679
Cited by
5
References
3
Citations by year
2026: 4 · 2025: 1
FWCI
3.29
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Nanomedicine (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders
  • Korea Health Industry Development Institute
  • National Research Foundation of Korea
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
pulmonary aspergillosis, itraconazole, polyvinyl alcohol, dry powder inhaler, pulmonary drug delivery, Aspergillus fumigatus, pulmonary targeting, hepatotoxicity, immunocompromised patients, spray drying, bronchoalveolar lavage fluid, antifungal therapy
MeSH terms
Administration, Inhalation, Animals, Antifungal Agents, Aspergillus fumigatus, Bronchoalveolar Lavage Fluid, Galactose, Lung, Male, Mannans, Polyvinyl Alcohol, Drug Delivery Systems, Rats, Sprague-Dawley, Itraconazole, Rats, Nanoparticles, Pulmonary Aspergillosis, Drug Liberation

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