Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Br J Ophthalmol. 2010 Feb;94(2):170-3. doi: 10.1136/bjo.2009.159541.
To determine the feasibility of macroesis for the delivery of ranibizumab and triamcinolone acetonide via a transcleral route.
Macroesis is a non-invasive method of drug delivery that uses alternating current (AC) to deliver drugs to target tissues. Two preclinical models of drug delivery were used for feasibility studies of delivering ranibizumab and triamcinolone acetonide to ocular tissues. In the first model, full-thickness sections of rabbit ocular tissue (conjunctiva to retina) were placed on an interdigitated electrode platform, and the drug was placed on the surface of the tissue. A non-uniform electrical field was applied to the ocular tissue, and electrical conductivity, a measurement of drug delivery, was monitored during the course of the experiment. In a second model, termed a 'simulated vitreous model,' the same full-thickness sections of rabbit ocular tissue were mounted below the electrode device, and the test compounds were placed on the electrodes. The fluid below the tissue, which simulated the vitreous cavity, was analysed using UV spectroscopy at the end of the study for the presence of drug.
In the electrical conductivity studies, the electric characteristics of the tissue-drug system clearly showed movement of the drug through the tissue to the dielectric sensor based on changes in the electrical conductivity of the tissue sample with triamcinolone. No change in tissue conductivity was observed when no drug was placed. No heat generation occurred during the course of the study; nor was any gross tissue destruction noted. In the simulated vitreous model, studies using triamcinolone yielded concentrations ranging from 0.280 to 0.970 mg/ml, depending on the voltage, frequency and time applied. In as little as 6.7 min, clinically efficacious doses could be obtained in the preclinical system. Studies using ranibizumab yielded concentrations of 0.070-0.171 mg/ml, depending on the voltage, frequency, and time applied. In as little at 6.7 min, 92.8% throughput could be achieved.
Successful delivery of ranibizumab and triamcinolone acetonide can be achieved with macroesis in preclinical studies.
确定经巩膜途径输送雷珠单抗和曲安奈德的巨量给药的可行性。
巨量给药是一种非侵入性的药物输送方法，它使用交流电 (AC) 将药物输送到靶组织。两种药物输送的临床前模型用于研究向眼部组织输送雷珠单抗和曲安奈德的可行性。在第一个模型中，将兔眼组织（从结膜到视网膜）的全厚切片放在叉指电极平台上，并将药物放在组织表面。在眼部组织上施加非均匀电场，并在实验过程中监测药物输送的电导率测量值。在第二个模型中，称为“模拟玻璃体模型”，将相同的兔眼全厚切片置于电极装置下方，并将测试化合物放置在电极上。研究结束时，使用紫外光谱法分析组织下方的模拟玻璃体腔中的流体中是否存在药物。
在电导率研究中，组织-药物系统的电学特性清楚地表明，药物通过组织向基于组织样品电导率变化的介电传感器移动，这是基于曲安奈德的。当没有放置药物时，组织的电导率没有变化。在研究过程中没有发生热产生，也没有观察到任何明显的组织破坏。在模拟玻璃体模型中，使用曲安奈德进行的研究产生了 0.280 至 0.970 mg/ml 之间的浓度，这取决于施加的电压、频率和时间。在 6.7 分钟内，在临床有效剂量可以在临床前系统中获得。使用雷珠单抗进行的研究产生了 0.070-0.171 mg/ml 的浓度，这取决于施加的电压、频率和时间。在 6.7 分钟内，可实现 92.8%的高通量。
在临床前研究中，使用巨量给药可以成功输送雷珠单抗和曲安奈德。
