Department of Ophthalmology, Faculty of Medicine, National University Hospital, University of Iceland, Reykjavik, Iceland; Department of Clinical Science, Ophthalmology, Umeå University, Umeå, Sweden.
Acta Ophthalmol. 2014 Sep;92(6):550-6. doi: 10.1111/aos.12334. Epub 2013 Dec 24.
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.
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(®) .
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).
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.
我们开发了纳米粒子γ-环糊精地塞米松（DexNP）和多佐胺（DorzNP）滴眼液，可在眼表面提供持续的高药物浓度。为了测试这些特性，我们在人类滴眼后测量了泪液中的地塞米松和多佐胺水平。
通过质谱法测量地塞米松的浓度。将一滴 DexNP 滴入一只眼睛。在滴眼后 7 个时间点用微毛细管吸移管采集泪液样品。对照眼接受 Maxidex（®）（地塞米松）。对于 DorzNP 和 Trusopt（®），用相同的程序进行多佐胺。
每组纳入 6 名受试者。DexNP 滴眼液（636.6 ± 399.1）的地塞米松峰值浓度（μg/ml ± 标准差）比 Maxidex（®）（39.3 ± 18.9）高 19 倍（p < 0.001）。在 4 小时时，DexNP 仍比 Maxidex（®）高 10 倍。此外，DexNP 使溶解的地塞米松在延长时间内的泪液中浓度增加约 30 倍，从而使更多的药物分配到眼组织中。DorzNP（59.5 ± 76.9）的多佐胺总浓度比 Trusopt（®）（40.0 ± 76.7）高约 50%（p < 0.05）。
结果表明 DexNP 具有高浓度和延长的溶解地塞米松浓度，这可以解释环糊精纳米颗粒药物传递平台中地塞米松的更大和更持久的作用。地塞米松似乎适合环糊精纳米颗粒悬浮液药物输送平台，其在泪液中的持续时间和浓度均高于现有商业滴眼剂，而多佐胺则不太适合。
