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从商业隐形眼镜中延长拉坦前列素释放:使用角膜模型的体外研究。

Extended latanoprost release from commercial contact lenses: in vitro studies using corneal models.

作者信息

Mohammadi Saman, Jones Lyndon, Gorbet Maud

机构信息

Systems Design Engineering, University of Waterloo, Waterloo, Ontario, Canada.

School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada; Centre for Contact Lens Research, University of Waterloo, Waterloo, Ontario, Canada.

出版信息

PLoS One. 2014 Sep 10;9(9):e106653. doi: 10.1371/journal.pone.0106653. eCollection 2014.

Abstract

In this study, we compared, for the first time, the release of a 432 kDa prostaglandin F2a analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution (131 μg = ml solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 μg of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 μg, was released, (p <0:001). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

摘要

在本研究中,我们首次使用含有角膜上皮细胞的体外模型,比较了市售隐形眼镜中432 kDa前列腺素F2α类似物药物拉坦前列素的释放情况。将传统的基于聚甲基丙烯酸羟乙酯(polyHEMA)的软性隐形眼镜和硅水凝胶软性隐形眼镜浸泡在药物溶液中(磷酸盐缓冲盐水中的溶液浓度为131μg/ml)。研究了药物从隐形眼镜材料中的释放及其通过三种体外模型的扩散情况。这三种体外模型包括:不含角膜上皮细胞的聚对苯二甲酸乙二酯(PET)膜、含有单层人角膜上皮细胞(HCEC)的PET膜以及含有分层HCEC的PET膜。在基于细胞的体外角膜上皮模型中,硅水凝胶材料实现了零级释放(在实验期间呈线性),48小时后,释放出4至6μg的拉坦前列素(该量完全在青光眼患者规定的每日剂量范围内)。在无细胞的情况下,释放的药物量显著较低,为0.3至0.5μg(p<0.001)。在有细胞和无细胞情况下,水凝胶镜片材料释放情况的差异强调了使用更能代表眼部生理状况的体外角膜模型来更充分地表征眼科给药材料的重要性。我们的结果表明,含有角膜上皮细胞的体外模型如何能够更好地预测体内释放情况。它还突出了药物浸泡型硅水凝胶隐形眼镜材料用于药物递送目的的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5856/4160170/4af2218eef20/pone.0106653.g001.jpg

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