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载三氯醋酸泼尼松龙的阳离子纳米类脂体制剂治疗葡萄膜炎:改善生物药剂学性能和抗炎活性的证据。

Triamcinolone acetonide loaded-cationic nano-lipoidal formulation for uveitis: Evidences of improved biopharmaceutical performance and anti-inflammatory activity.

机构信息

University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India.

Institute of Inflammation & Ageing, University of Birmingham, Birmingham, B15 2TT, UK.

出版信息

Colloids Surf B Biointerfaces. 2020 Jun;190:110902. doi: 10.1016/j.colsurfb.2020.110902. Epub 2020 Feb 25.

DOI:10.1016/j.colsurfb.2020.110902
PMID:32143010
Abstract

Topical administration of corticosteroids is the cornerstone treatment of anterior uveitis, but poor corneal penetration and retention cause hindrance in their therapeutic utility. The conventional eye drops are less valuable in conditions where inflammation reaches deeper regions of the eye. Therefore, there is a clear need for an effective drug delivery system, which can increase corticosteroid penetration after topical application. To address this, cationic nanostructured lipid carriers of the drug triamcinolone acetonide (cTA-NLC) were prepared. The cTA-NLC were prepared by a hot microemulsion method and evaluated for drug release, permeation, cell uptake, cytotoxicity, anti-inflammatory activity and ocular irritancy. The cTA-NLC are nanometric in size (< 200 nm), with a zeta potential of about +35 mv and % drug EE of 88 %. The nanocarriers exhibited slow and sustained release of around 84 % in 24 h and transcorneal drug permeation of 51 % in 8 h. The nanocarriers exhibited no cytotoxicity (% cell viability of>90 %). The cell uptake study showed that nanocarriers could retain inside the cells for 24 h. The developed formulation could significantly reduce the TNF-α level in LPS induced inflamed cells. The studies indicated that cTA-NLC could be a promising option for the topical treatment of uveitis.

摘要

皮质类固醇的局部给药是前葡萄膜炎的基础治疗方法,但角膜穿透和滞留能力差会阻碍其治疗效果。在炎症到达眼睛更深部位的情况下,传统的眼药水效果较差。因此,非常需要一种有效的药物传递系统,以增加局部应用后的皮质类固醇穿透。为了解决这个问题,制备了曲安奈德(cTA)的阳离子纳米结构脂质载体(cTA-NLC)。通过热微乳液法制备 cTA-NLC,并对其药物释放、渗透、细胞摄取、细胞毒性、抗炎活性和眼刺激性进行了评价。cTA-NLC 的尺寸小于 200nm(<200nm),zeta 电位约为+35mv,药物 EE%为 88%。纳米载体在 24 小时内可缓慢持续释放约 84%,在 8 小时内可透过角膜渗透 51%的药物。纳米载体无细胞毒性(>90%的细胞活力)。细胞摄取研究表明,纳米载体可以在细胞内保留 24 小时。所开发的制剂可显著降低 LPS 诱导的炎症细胞中 TNF-α的水平。这些研究表明,cTA-NLC 可能是治疗葡萄膜炎的一种有前途的局部治疗选择。

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