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

Marcus Hill, Matthew Twigg, Emer Sheridan, John Hardy , Stuart Elborn, Cliff Taggart, Christopher Scott, Marie Migaud

Research output: Contribution to journalArticle

Abstract

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 Pseudomonas aeruginosa 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 P. aeruginosa 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 P. aeruginosa 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.
LanguageEnglish
Number of pages12
JournalPharmaceutics
Volume11
Issue number8
DOIs
Publication statusPublished - 2 Aug 2019

Fingerprint

Tobramycin
Chitosan
Mucus
Drug Delivery Systems
Cystic Fibrosis
Pseudomonas aeruginosa
Lung
Secretory Leukocyte Peptidase Inhibitor
Pseudomonas Infections
Leukocyte Elastase
Infection
Anti-Bacterial Agents
Therapeutics
alginic acid
colistinmethanesulfonic acid
In Vitro Techniques

Keywords

  • BIOMEDICAL APPLICATIONS
  • Drug Delivery Systems
  • Particles
  • Antimicrobial

Cite this

Hill, Marcus ; Twigg, Matthew ; Sheridan, Emer ; Hardy , John ; Elborn, Stuart ; Taggart, Cliff ; Scott, Christopher ; Migaud, Marie. / Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications. In: Pharmaceutics. 2019 ; Vol. 11, No. 8.
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abstract = "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 Pseudomonas aeruginosa 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 P. aeruginosa 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 P. aeruginosa 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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Hill, M, Twigg, M, Sheridan, E, Hardy , J, Elborn, S, Taggart, C, Scott, C & Migaud, M 2019, 'Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications', Pharmaceutics, vol. 11, no. 8. https://doi.org/10.3390/pharmaceutics11080379

Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications. / Hill, Marcus; Twigg, Matthew; Sheridan, Emer; Hardy , John; Elborn, Stuart; Taggart, Cliff; Scott, Christopher; Migaud, Marie.

In: Pharmaceutics, Vol. 11, No. 8, 02.08.2019.

Research output: Contribution to journalArticle

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AU - Hill, Marcus

AU - Twigg, Matthew

AU - Sheridan, Emer

AU - Hardy , John

AU - Elborn, Stuart

AU - Taggart, Cliff

AU - Scott, Christopher

AU - Migaud, Marie

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N2 - 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 Pseudomonas aeruginosa 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 P. aeruginosa 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 P. aeruginosa 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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