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

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.

Citation
Ornelas-Megiatto, C., Shah, P. N., Wich, P. R., Cohen, J. L., Tagaev, J. A., Smolen, J. A., … Cannon, C. L. (2012). Aerosolized Antimicrobial Agents Based on Degradable Dextran Nanoparticles Loaded with Silver Carbene Complexes. Molecular Pharmaceutics, 9(11), 3012–3022. doi:10.1021/mp3004379

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.

Publisher
American Chemical Society (ACS)

Journal
Molecular Pharmaceutics

DOI
10.1021/mp3004379

PubMed ID
23025592

PubMed Central ID
PMC3579655

Additional Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579655http://europepmc.org/articles/pmc3579655?pdf=render

Permanent link to this record