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Junjie Zhang, Liya Wang, Tianyang Zhou, Jijun He, Huiyun Xia, Hongmin Zhang, Shengtao Sun, Xiaohua Li; Novel natamycin ocular drug delivery system enhanced the ocular penetration after topically applied to rabbits. Invest. Ophthalmol. Vis. Sci. 2014;55(13):459.
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© ARVO (1962-2015); The Authors (2016-present)
The current natamycin (NAT) formulation consists of 5% (w/v) ophthalmic suspension. The poor bioavailability of suspension eye drop is due to poor permeability of cornea, etc., thus, causing marketed eye drops often less efficacious. We developed a novel NAT (0.5%) ocular drug delivery system (NATE) as an attempt to improve its penetration and availability in ocular tissues. Ocular pharmacokinetics were evaluated after topically applied.
A single dose of either 0.5% NATE or commercially available 5% NAT Suspension (NATS) was applied to rabbits with intact epithelium cornea, respectively. Corneas were collected at predetermined time points. The corneas in a second set of rabbits were anesthetized and then chemically abraded with 6.5mm diameter using 50% ethanol before receiving the same dosing regimens as in the groups with intact corneas. NAT levels in the corneas were assayed using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) analysis.
In the intact epithelium cornea group: the NAT levels in cornea in NATE group were significantly higher than in NATS group at corresponding time points (p < 0.05). Maximum NAT levels were achieved in the corneas in NATE and NATS group at 15 and 30 minutes, respectively, in the intact epithelium eyes (0.85 ± 0.28 and 0.28 ± 0.16 μg/g, respectively, mean ± SEM, n = 6). The AUC0-360 (area under the concentration-time curve between 0 and 360 min) in corneas for NATE and NATS group were 105.87 and 59.23 μg/g*min, respectively. In the deepithelium eyes group: at predetermined time points 15, 30, 60, and 120 minutes, NAT levels in corneas in NATE group were 11.30 ± 1.25, 8.21± 2.40, 5.74± 1.67 and 1.86 ± 0.67 μg/g, were 9.2, 9.9, 9.0 and 4.9-fold higher than in NATS group at the corresponding time points, respectively. Maximum NAT levels were achieved in the corneas in NATE and NATS group both at 15 minutes in the deepithelium eyes (11.30 ± 1.25.0 and 1.23 ± 0.36 μg/g, respectively). The AUC0-360 in corneas for NATE and NATS group were 812.40 and 118.70 μg/g*min, respectively for the deepithelium eyes group. NAT levels in plasma in deepithelium eyes group were below the low detection limit (5ng/ml) after topically application of NATE or NATS.
The novel NAT ocular delivery system can significantly increase the drug corneal penetration and ocular bioavailability after topically applied.
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