RT Journal Article
SR Electronic
T1 Formulation of dual modality nanoparticles to enhance tobramycin efficacy in cystic fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 224
VO 42
IS Suppl 57
A1 Jill Deacon
A1 Sharif Abdelghany
A1 Stuart Elborn
A1 Adrien Kissenpfennig
A1 Clifford Taggart
A1 Christopher Scott
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/224.abstract
AB IntroductionCystic fibrosis (CF) patients aberrantly produce viscous mucus in their lungs, which acts as a penetrative barrier to antibiotic delivery and provides an ideal environment for bacterial colonisation.Aims and ObjectivesThe aim is to develop a nanoparticle drug delivery system combining widely used CF therapeutics for an enhanced antibiotic effect. Tobramycin is an aminoglycoside antibiotic and the mucolytic DNase thins viscous secretions. For this study, it was hypothesised that alginate/chitosan nanoparticles (NPs) loaded with tobramycin and functionalised with DNase would enhance penetration of tobramycin to the site of infection within the mucus.MethodsTobramycin loaded alginate/chitosan NPs were formulated by ionotropic gelation and conjugated with DNase on their surface. NP formulation was optimised and CF sputum samples were tested with NPs to establish bactericidal effects against Pseudomonas aeruginosa.ResultsNPs formed at around 500 nm and were loaded with tobramycin 89µg/mg polymer and DNase 19µg/mg polymer. Activity of both modalities was confirmed against in vitro cultures of P. aeruginosa and by cleavage of DNA (plasmid and CF sputum samples). Treatment of CF sputum with DNase-tobramycin NPs resulted in reduced viscosity and increased bacterial killing in these samples.ConclusionThese novel alginate/chitosan NPs combining DNase and tobramycin are an effective antibacterial treatment in CF sputum. The incorporation of two widely used therapeutics into a single formulation provides promise in the future treatment regimen of CF patients.