Local inflammation alters the lung disposition of a drug loaded pegylated liposome after pulmonary dosing to rats.
J Control Release
; 307: 32-43, 2019 08 10.
Article
em En
| MEDLINE
| ID: mdl-31152749
ABSTRACT
The development of inhalable 'nanomedicines' based on biocompatible lipids and polymers is attracting increasing interest worldwide. Our understanding of how pulmonary inflammation impacts on lung distribution and clearance kinetics however, is limited. Similarly, there is limited information on how the inhaled delivery of biocompatible nanomaterials affects existing respiratory disease. We have addressed these knowledge gaps by describing and comparing the pulmonary pharmacokinetic behaviour of a 3H-labelled PEGylated liposome loaded with a model drug (ciprofloxacin) after intratracheal administration to healthy rats and rats with bleomycin-induced lung inflammation by following both 3H label and drug. Cell- and cytokine-based markers of lung inflammation were used to evaluate the response of healthy and inflamed lungs to the liposome. Liposomes were initially cleared more rapidly from inflamed lungs than from healthy lungs, but exhibited similar rates of lung clearance after 3â¯days. This was interesting given that mucociliary clearance was more efficient from healthy lungs, despite evidence of higher mucus retention in inflamed lungs and reduced association of the liposome with lung tissue. Although the plasma pharmacokinetics of ciprofloxacin did not differ between rats with healthy or inflamed lungs after pulmonary administration, the plasma pharmacokinetics of 3H-phosphatidylcholine suggested higher liposome bioavailability and more prolonged absorption from inflamed lungs. Concentrations of the pro-inflammatory cytokine IL-1ß were increased in bronchoalveolar lavage fluid after a single pulmonary dose of liposomes to rats with inflamed lungs, but no other significant changes in lung inflammatory markers were identified in healthy or bleomycin-challenged rats.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Ciprofloxacina
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Inflamação
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Pulmão
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Pneumopatias
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Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
J Control Release
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália