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脂质纳米载体:提高亲水性药物(伐昔洛韦)眼部递药效率的新方法

Lipid Nanocarrier: an Efficient Approach Towards Ocular Delivery of Hydrophilic Drug (Valacyclovir).

机构信息

UIPS, Panjab University, Chandigarh, 160014, India.

出版信息

AAPS PharmSciTech. 2017 Apr;18(3):884-894. doi: 10.1208/s12249-016-0575-2. Epub 2016 Jul 1.

Abstract

This research focuses on the fabrication and evaluation of solid lipid nanoparticles (SLNs) for improved ocular delivery of valacyclovir (VAC). Stearic acid and tristearin were selected as the lipid carrier while Poloxamer 188 and sodium taurocholate were used as surfactant and co-surfactant, respectively. The physiochemical properties of the optimized batch (SLN-6) fulfil the prerequisites needed for an ideal ocular formulation like submicron size (202.5 ± 2.56 nm), narrow PDI (0.252 ± 0.06), high zeta potential (-34.4 ± 3.04 mV) and good entrapment efficiency (58.82 ± 2.45%). The in vitro release study of SLN-6 exhibited a sustained release profile (>60% in 12 h). The ex vivo studies performed on excised cornea exhibited enhanced drug permeation of SLNs (22.17 ± 1.41 μg/cm h) in comparison to the drug solution (3.78 ± 1.34 μg/cm h). Apart, the corneal hydration studies, histopathology and Hen's Egg Test Chorio Allantoic Membrane (HETCAM) assay, confirmed the non-irritancy of SLNs. The in vivo study confirmed improved ocular bioavailability of VAC from SLN-6 (AUC: 856.47 ± 7.86 μg h/mL) in contrast to the drug solution (AUC: 470.75 ± 8.91 μg h/mL). Hence, the overall studies suggested the potential of SLNs in efficient ocular delivery of a hydrophilic molecule like VAC.

摘要

本研究专注于制备和评估固体脂质纳米粒(SLN),以改善伐昔洛韦(VAC)的眼部递药。硬脂酸和三硬脂酸甘油酯被选为脂质载体,而泊洛沙姆 188 和牛磺胆酸钠分别用作表面活性剂和助表面活性剂。优化批次(SLN-6)的理化性质满足理想眼部制剂的先决条件,如亚微米级大小(202.5±2.56nm)、较窄的 PDI(0.252±0.06)、高 ζ 电位(-34.4±3.04mV)和良好的包封效率(58.82±2.45%)。SLN-6 的体外释放研究显示出持续释放的特征(12 小时内超过 60%)。在离体角膜上进行的体外研究显示,与药物溶液(3.78±1.34μg/cm h)相比,SLN 表现出增强的药物渗透(22.17±1.41μg/cm h)。此外,角膜水化研究、组织病理学和鸡胚绒毛尿囊膜(HETCAM)试验证实了 SLN 的非刺激性。体内研究证实,与药物溶液(AUC:470.75±8.91μg h/mL)相比,SLN-6 提高了 VAC 的眼部生物利用度(AUC:856.47±7.86μg h/mL)。因此,总体研究表明,SLN 具有将亲水分子如 VAC 高效递送至眼部的潜力。

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