Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications

Cystic fibrosis (CF) is a complex, potentially life-threatening disease that is most effectively treated through the administration of antibiotics (e.g., colistimethate sodium). Chronic infection with <i>Pseudomonas aeruginosa</i> is one of the most significant events in the pathogenesis...

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Main Authors: Marcus Hill, Matthew Twigg, Emer A. Sheridan, John G. Hardy, J. Stuart Elborn, Clifford C. Taggart, Christopher J. Scott, Marie E. Migaud
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/11/8/379
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author Marcus Hill
Matthew Twigg
Emer A. Sheridan
John G. Hardy
J. Stuart Elborn
Clifford C. Taggart
Christopher J. Scott
Marie E. Migaud
author_facet Marcus Hill
Matthew Twigg
Emer A. Sheridan
John G. Hardy
J. Stuart Elborn
Clifford C. Taggart
Christopher J. Scott
Marie E. Migaud
author_sort Marcus Hill
collection DOAJ
description Cystic fibrosis (CF) is a complex, potentially life-threatening disease that is most effectively treated through the administration of antibiotics (e.g., colistimethate sodium). Chronic infection with <i>Pseudomonas aeruginosa</i> is one of the most significant events in the pathogenesis of cystic fibrosis, and tobramycin is the treatment of choice for those patients with chronic <i>P. aeruginosa</i> infection who are deteriorating despite regular administration of colistimethate sodium. Effective treatment can be challenging due to the accumulation of thickened mucus in the pulmonary environment, and here we describe the results of our investigation into the development of alginate/chitosan particles prepared via precipitation for such environments. Tobramycin loading and release from the alginate/chitosan particles was investigated, with evidence of both uptake and release of sufficient tobramycin to inhibit <i>P. aeruginosa</i> in vitro. Functionalisation of the alginate/chitosan particles with secretory leukocyte protease inhibitor (SLPI) was shown to help inhibit the inflammatory response associated with lung infections (via inhibition of neutrophil elastase activity) and enhance their interaction with cystic fibrosis mucus (assayed via reduction of the depth of particle penetration into the mucus) in vitro, which have prospects to enhance their efficacy in vivo.
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spelling doaj.art-40bbb02fdf184fd09e2262181221e3622022-12-22T03:59:16ZengMDPI AGPharmaceutics1999-49232019-08-0111837910.3390/pharmaceutics11080379pharmaceutics11080379Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary ApplicationsMarcus Hill0Matthew Twigg1Emer A. Sheridan2John G. Hardy3J. Stuart Elborn4Clifford C. Taggart5Christopher J. Scott6Marie E. Migaud7School of Pharmacy, Queen’s University Belfast Queen’s University Belfast, Belfast BT7 1NN, UKAirway Innate Immunity Group (AiiR), Wellcome Wolfson Institute of Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UKLancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Sharoe Green Lane PR2 9HT, UKDepartment of Chemistry, Lancaster University, Lancaster, Lancashire LA1 4YB, UKSchool of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UKAirway Innate Immunity Group (AiiR), Wellcome Wolfson Institute of Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UKCentre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UKSchool of Pharmacy, Queen’s University Belfast Queen’s University Belfast, Belfast BT7 1NN, UKCystic fibrosis (CF) is a complex, potentially life-threatening disease that is most effectively treated through the administration of antibiotics (e.g., colistimethate sodium). Chronic infection with <i>Pseudomonas aeruginosa</i> is one of the most significant events in the pathogenesis of cystic fibrosis, and tobramycin is the treatment of choice for those patients with chronic <i>P. aeruginosa</i> infection who are deteriorating despite regular administration of colistimethate sodium. Effective treatment can be challenging due to the accumulation of thickened mucus in the pulmonary environment, and here we describe the results of our investigation into the development of alginate/chitosan particles prepared via precipitation for such environments. Tobramycin loading and release from the alginate/chitosan particles was investigated, with evidence of both uptake and release of sufficient tobramycin to inhibit <i>P. aeruginosa</i> in vitro. Functionalisation of the alginate/chitosan particles with secretory leukocyte protease inhibitor (SLPI) was shown to help inhibit the inflammatory response associated with lung infections (via inhibition of neutrophil elastase activity) and enhance their interaction with cystic fibrosis mucus (assayed via reduction of the depth of particle penetration into the mucus) in vitro, which have prospects to enhance their efficacy in vivo.https://www.mdpi.com/1999-4923/11/8/379biomedical applicationsdrug delivery systemsparticlesantimicrobial
spellingShingle Marcus Hill
Matthew Twigg
Emer A. Sheridan
John G. Hardy
J. Stuart Elborn
Clifford C. Taggart
Christopher J. Scott
Marie E. Migaud
Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications
Pharmaceutics
biomedical applications
drug delivery systems
particles
antimicrobial
title Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications
title_full Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications
title_fullStr Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications
title_full_unstemmed Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications
title_short Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications
title_sort alginate chitosan particle based drug delivery systems for pulmonary applications
topic biomedical applications
drug delivery systems
particles
antimicrobial
url https://www.mdpi.com/1999-4923/11/8/379
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