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一种新型0.005%拉坦前列素眼用纳米乳剂:细胞毒性研究。

A novel ophthalmic latanoprost 0.005% nanoemulsion: a cytotoxicity study.

作者信息

Tau Julia, Passerini María Silvia, Del Papa Melina, Aguilar Alejandro, Berra Alejandro

机构信息

Uriburu 950,Laboratory of Ocular Research, Department of Pathology, Faculty of Medicine, University of Buenos Aires, C1114AAD, Buenos Aires, Argentina.

Medical Affairs. Poen Laboratories S.A.U., Gómez de Fonseca 652, CABA, C1407BDR, Buenos Aires, Argentina.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2022 Jun;260(6):1941-1946. doi: 10.1007/s00417-021-05536-y. Epub 2022 Jan 11.

Abstract

BACKGROUND

Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK.

METHODS

Two different latanoprost eye drops were used: one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60 min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V-FITC and propidium iodide.

RESULTS

The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (p < 0.05 at 15 and 30 min; p < 0.01 at 60 min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe.

CONCLUSIONS

The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

摘要

背景

苯扎氯铵(BAK)是抗青光眼滴眼液中最常用的防腐剂,会对眼表造成损害。已研发出一种避免使用BAK的新型抗青光眼制剂。本研究的目的是评估该制剂的细胞毒性,并将其与含BAK的眼药水进行比较。

方法

使用两种不同的拉坦前列素滴眼液:一种是含0.02% BAK的眼药水(LSc),另一种是含软防腐剂(0.18%山梨酸钾)的眼用纳米乳剂(LNe)。将人结膜上皮细胞分别与LSc或LNe孵育15、30和60分钟。通过MTT法测定细胞毒性。使用膜联蛋白V-FITC和碘化丙啶通过流式细胞术测量细胞死亡情况。

结果

与对照组相比,暴露于LNe的细胞获得的细胞活力和增殖值在80%至90%之间,而在所有研究时间点,暴露于LSc的细胞获得的值约为30%(15和30分钟时p<0.05;60分钟时p<0.01)。在所有研究时间点,与用LNe孵育的细胞相比,用LSc孵育的细胞中活细胞百分比显著降低,而与LNe相比,暴露于LSc的细胞中晚期凋亡/坏死细胞百分比显著增加。

结论

新型拉坦前列素纳米乳剂对人结膜细胞的细胞毒性明显低于LSc。这些结果表明,新制剂对眼表的刺激性可能比目前可用的含BAK的拉坦前列素溶液更小。

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