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

Handle URI:
http://hdl.handle.net/10754/562399
Title:
Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes
Authors:
Ornelas-Megiatto, Cátia; Shah, Parth N.; Wich, Peter R.; Cohen, Jessica L.; Tagaev, Jasur A.; Smolen, Justin A.; Wright, Brian D.; Panzner, Matthew J.; Youngs, Wiley J.; Frechet, Jean ( 0000-0001-6419-0163 ) ; Cannon, Carolyn L.
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.
KAUST Department:
Chemical Science Program; Physical Sciences and Engineering (PSE) Division
Publisher:
American Chemical Society (ACS)
Journal:
Molecular Pharmaceutics
Issue Date:
5-Nov-2012
DOI:
10.1021/mp3004379
PubMed ID:
23025592
PubMed Central ID:
PMC3579655
Type:
Article
ISSN:
15438384
Sponsors:
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.
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579655
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; Chemical Science Program

Full metadata record

DC FieldValue Language
dc.contributor.authorOrnelas-Megiatto, Cátiaen
dc.contributor.authorShah, Parth N.en
dc.contributor.authorWich, Peter R.en
dc.contributor.authorCohen, Jessica L.en
dc.contributor.authorTagaev, Jasur A.en
dc.contributor.authorSmolen, Justin A.en
dc.contributor.authorWright, Brian D.en
dc.contributor.authorPanzner, Matthew J.en
dc.contributor.authorYoungs, Wiley J.en
dc.contributor.authorFrechet, Jeanen
dc.contributor.authorCannon, Carolyn L.en
dc.date.accessioned2015-08-03T10:03:49Zen
dc.date.available2015-08-03T10:03:49Zen
dc.date.issued2012-11-05en
dc.identifier.issn15438384en
dc.identifier.pmid23025592en
dc.identifier.doi10.1021/mp3004379en
dc.identifier.urihttp://hdl.handle.net/10754/562399en
dc.description.abstractDegradable 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.en
dc.description.sponsorshipThis 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.en
dc.publisherAmerican Chemical Society (ACS)en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579655en
dc.subjectAc-DEX particlesen
dc.subjectantimicrobialen
dc.subjectdegradableen
dc.subjectdextranen
dc.subjectpulmonary diseasesen
dc.subjectsilver carbene complexesen
dc.titleAerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexesen
dc.typeArticleen
dc.contributor.departmentChemical Science Programen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.identifier.journalMolecular Pharmaceuticsen
dc.identifier.pmcidPMC3579655en
dc.contributor.institutionCollege of Chemistry, 718 Latimer Hall, University of California, Berkeley, Berkeley, CA 94720-1460, United Statesen
dc.contributor.institutionDivision of Pulmonary and Vascular Biology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX 75390-9063, United Statesen
dc.contributor.institutionDepartment of Chemistry, University of Akron, Akron, OH 44325-0002, United Statesen
kaust.authorFrechet, Jeanen

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