UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
UCL Department of Chemistry, University College London, 20 Gordon St, London WC1H 0AJ, UK.
J Mater Chem B. 2020 Aug 19;8(32):7264-7274. doi: 10.1039/d0tb01033b.
Magnetic resonance imaging (MRI) is one of the most widely-used non-invasive clinical imaging tools, producing detailed anatomical images whilst avoiding side effects such as trauma or X-ray radiation exposure. In this article, a new approach to non-invasive monitoring of drug release from a delivery vehicle via MRI was developed, using pH-responsive Eudragit L100 and S100 fibres encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) and carmofur (a drug used in the treatment of colon cancer). Fibres were prepared by electrospinning, and found to be smooth and cylindrical with diameters of 645 ± 225 nm for L100 and 454 ± 133 nm for S100. The fibres exhibited pH responsive dissolution behaviour. Around the physiological pH range, clear pH-responsive proton relaxation rate changes due to matrix swelling/dissolution can be observed: r2 values of L100 fibres increase from 29.3 ± 8.3 to 69.8 ± 2.5 mM-1 s-1 over 3 h immersion in a pH 7.4 medium, and from 13.5 ± 2.0 mM-1 s-1 to 42.1 ± 3.0 mM-1 s-1 at pH 6.5. The r2 values of S100 fibres grow from 30.4 ± 4.4 to 64.7 ± 1.0 mM-1 s-1 at pH 7.4, but at pH 6.5, where the S100 fibres are not soluble, r2 remains very low (< 4 mM-1 s-1). These dramatic changes in relaxivity demonstrate that pH-responsive dissolution results in SPION release. In vitro drug release studies showed the formulations gave rapid release of carmofur at physiological pH values (pH 6.5 and 7.4), and acid stability studies revealed that they can protect the SPIONs from digestion in acid environments, giving the fibres potential for oral administration. Exploration of the relationship between relaxivity and carmofur release suggests a linear correlation (R2 > 0.94) between the two. Mathematical equations were developed to predict carmofur release in vitro, with very similar experimental and predicted release profiles obtained. Therefore, the formulations developed herein have the potential to be used for non-invasive monitoring of drug release in vivo, and could ultimately result in dramatic reductions to off-target side effects from interventions such as chemotherapy.
磁共振成像（MRI）是最广泛使用的非侵入性临床成像工具之一，它可以生成详细的解剖图像，同时避免创伤或 X 射线辐射等副作用。在本文中，我们开发了一种新的方法，通过 MRI 对药物从载体中的释放进行非侵入性监测，该方法使用 pH 响应性 Eudragit L100 和 S100 纤维包封超顺磁氧化铁纳米粒子（SPIONs）和卡莫氟（一种用于治疗结肠癌的药物）。纤维通过静电纺丝制备，发现其具有光滑的圆柱形，L100 的直径为 645 ± 225nm，S100 的直径为 454 ± 133nm。纤维表现出 pH 响应性的溶解行为。在生理 pH 范围内，可以观察到由于基质溶胀/溶解引起的明显的 pH 响应质子弛豫率变化：在 pH 7.4 介质中浸泡 3 小时后，L100 纤维的 r2 值从 29.3 ± 8.3 增加到 69.8 ± 2.5 mM-1 s-1，在 pH 6.5 时从 13.5 ± 2.0 mM-1 s-1 增加到 42.1 ± 3.0 mM-1 s-1。S100 纤维的 r2 值在 pH 7.4 时从 30.4 ± 4.4 增加到 64.7 ± 1.0 mM-1 s-1，但在 pH 6.5 时，由于 S100 纤维不溶，r2 值仍然非常低（<4 mM-1 s-1）。弛豫率的这些剧烈变化表明 pH 响应性溶解导致 SPION 释放。体外药物释放研究表明，这些制剂在生理 pH 值（pH 6.5 和 7.4）下快速释放卡莫氟，酸稳定性研究表明它们可以保护 SPION 免受酸性环境中的消化，使纤维具有口服给药的潜力。弛豫率与卡莫氟释放之间关系的探索表明两者之间存在线性相关（R2 > 0.94）。开发了数学方程来预测体外卡莫氟的释放，得到了非常相似的实验和预测的释放曲线。因此，本文开发的制剂有可能用于体内药物释放的非侵入性监测，并最终可能会大大降低化疗等干预措施的非靶向副作用。
