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Enhanced pulmonary delivery of fluticasone propionate in rodents by mucus-penetrating nanoparticles.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2016 Apr 11; Vol. 502 (1-2), pp. 188-97. Date of Electronic Publication: 2016 Feb 20. - Publication Year :
- 2016
-
Abstract
- Most attempts to achieve sustained drug delivery to pulmonary tissues using nanoparticles have focused on mucoadhesive particles (MAP). However, MAP become trapped in the luminal mucus layer and, as a result, are largely eliminated from the respiratory tract by mucociliary escalator and expiratory clearance, which undermines their sustained release potential. Recent studies have shown that mucus-penetrating particles (MPP) engineered to diffuse through mucus can avoid rapid mucociliary clearance in vivo and persist in the lung longer. Nonetheless, it has not been confirmed that MPP encapsulating small molecules can sustain drug release in the lung longer than MAP of similar size and core composition. As a proof of concept, we encapsulated fluticasone propionate (FP) into poly(lactide)-based MPP and MAP (both ∼ 200 nm diameter, ∼ 30-35% drug loading) and evaluated their pulmonary residence by measuring FP levels in mouse lungs over 24h following intratracheal instillation. Furthermore, we evaluated the duration of action of FP MPP in a rat lung inflammation model compared to that of a non-encapsulated FP control. In rodents, pulmonary delivery of FP formulated as MPP provided a 60% higher local exposure compared to MAP and extended the single dose efficacy by at least 16 h compared to non-encapsulated FP.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Inhalation
Animals
Anti-Inflammatory Agents chemistry
Anti-Inflammatory Agents pharmacokinetics
Anti-Inflammatory Agents therapeutic use
Delayed-Action Preparations administration & dosage
Delayed-Action Preparations chemistry
Delayed-Action Preparations pharmacokinetics
Delayed-Action Preparations therapeutic use
Female
Fluticasone chemistry
Fluticasone pharmacokinetics
Fluticasone therapeutic use
Humans
Inflammation chemically induced
Inflammation drug therapy
Inflammation metabolism
Lipopolysaccharides
Lung metabolism
Lung Diseases
Male
Mice
Nanoparticles chemistry
Polyesters chemistry
Rats, Inbred Lew
Anti-Inflammatory Agents administration & dosage
Drug Delivery Systems
Fluticasone administration & dosage
Mucus metabolism
Nanoparticles administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 502
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 26902722
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2016.02.031