Premium
Kinetics of γ ‐cyclodextrin nanoparticle suspension eye drops in tear fluid
Author(s) -
Jóhannesson Gauti,
MoyaOrtega Maria D.,
Ásgrímsdóttir Gudrún Marta,
Lund Sigrún H.,
Thorsteinsdóttir Margrét,
Loftsson Thorsteinn,
Stefánsson Einar
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.12334
Subject(s) - dexamethasone , dorzolamide , eye drop , chemistry , cyclodextrin , chromatography , medicine , ophthalmology , endocrinology , intraocular pressure , timolol
Purpose We have developed nanoparticle γ ‐cyclodextrin dexamethasone ( D ex NP ) and dorzolamide ( D orz NP ) 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 D ex NP was instilled into one eye. Tear fluid was sampled with microcapillary pipettes at seven time‐points after drop instillation. Control eyes received M axidex ® (dexamethasone). The same procedure was performed for dorzolamide with D orz NP and T rusopt ® . Results Six subjects were included in each group. The peak concentration ( μ g/ml ± standard deviation) of dexamethasone for Dex NP 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, D ex NP was still 10 times higher than M axidex ® . In addition, D ex NP 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 D orz NP (59.5 ± 76.9) than T rusopt ® (40.0 ± 76.7) (p < 0.05). Conclusion The results indicate high and extended concentration of dissolved dexamethasone with D ex NP , 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.