title: Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid.
abstract: OBJECTIVE
  We have developed nanoparticle γ-cyclodextrin dexamethasone (DexNP) and dorzolamide (DorzNP) eye drops that provide sustained high drug concentrations on the eye surface. To test these characteristics, we measured dexamethasone and dorzolamide levels in tear fluid in humans following eye drop administration.
  
  
  METHODS
  Concentration of dexamethasone was measured by mass spectrometry. One drop of DexNP was instilled into one eye. Tear fluid was sampled with microcapillary pipettes at seven time-points after drop instillation. Control eyes received Maxidex(®) (dexamethasone). The same procedure was performed for dorzolamide with DorzNP and Trusopt(®) .
  
  
  RESULTS
  Six subjects were included in each group. The peak concentration (μg/ml ± standard deviation) of dexamethasone for DexNP eye drops (636.6 ± 399.1) was up to 19-fold higher than with Maxidex(®) (39.3 ± 18.9) (p < 0.001). At 4 hr, DexNP was still 10 times higher than Maxidex(®) . In addition, DexNP resulted in about 30-fold higher concentration of dissolved dexamethasone in the tear fluid of extended time period allowing more drug to partition into the eye tissue. The overall concentration of dorzolamide was about 50% higher for DorzNP (59.5 ± 76.9) than Trusopt(®) (40.0 ± 76.7) (p < 0.05).
  
  
  CONCLUSIONS
  The results indicate high and extended concentration of dissolved dexamethasone with DexNP, which can explain the greater and longer lasting effect of dexamethasone in the cyclodextrin nanoparticle drug delivery platform. Dexamethasone seems to fit the cyclodextrin nanoparticle suspension drug delivery platform with longer duration and higher concentrations in tear fluid than available commercial drops, while dorzolamide is less suitable.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, National University Hospital, University of Iceland, Reykjavik, Iceland; Department of Clinical Science, Ophthalmology, Umeå University, Umeå, Sweden.
authors.forename: Gauti
authors.initials: G
authors.lastname: Jóhannesson
authors.forename: Maria D
authors.initials: MD
authors.lastname: Moya-Ortega
authors.forename: Gudrún Marta
authors.initials: GM
authors.lastname: Ásgrímsdóttir
authors.forename: Sigrún H
authors.initials: SH
authors.lastname: Lund
authors.forename: Margrét
authors.initials: M
authors.lastname: Thorsteinsdóttir
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
authors.forename: Einar
authors.initials: E
authors.lastname: Stefánsson
mesh_terms: D001682:Biological Availability; D002257:Carbonic Anhydrase Inhibitors / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D013449:Sulfonamides / Q000493:pharmacokinetics*; D013535:Suspensions; D053719:Tandem Mass Spectrometry; D013666:Tears / Q000378:metabolism*; D013876:Thiophenes / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D047408:gamma-Cyclodextrins / Q000493:pharmacokinetics*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013535:Suspensions; D013876:Thiophenes; D047408:gamma-Cyclodextrins; D003907:Dexamethasone; C062765:dorzolamide
keywords: Maxidex; Trusopt; cyclodextrin nanoparticles; dexamethasone; dorzolamide; tear fluid