Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes

Cátia Ornelas-Megiatto, Parth N. Shah, Peter R. Wich, Jessica L. Cohen, Jasur A. Tagaev, Justin A. Smolen, Brian D. Wright, Matthew J. Panzner, Wiley J. Youngs, Jean Frechet, Carolyn L. Cannon

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH2Cl2 (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery. © 2012 American Chemical Society.
Original languageEnglish (US)
Pages (from-to)3012-3022
Number of pages11
JournalMolecular Pharmaceutics
Volume9
Issue number11
DOIs
StatePublished - Oct 1 2012

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This project has been funded in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN268201000043C, and in part through the Frechet "various gifts" fund for the support of research in new materials. P.R.W. gratefully acknowledges the Alexander von Humboldt Foundation (AvH) for funding.

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science
  • Molecular Medicine

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