Jin Miao, Yu Deng-Guang, Geraldes Carlos F G C, Williams Gareth R, Bligh S W Annie
UCL School of Pharmacy, University College London , 29-39 Brunswick Square, London WC1N 1AX, U.K.
School of Materials Science & Engineering, University of Shanghai for Science and Technology , Shanghai 200093, China.
Mol Pharm. 2016 Jul 5;13(7):2457-65. doi: 10.1021/acs.molpharmaceut.6b00197. Epub 2016 Jun 20.
New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core-shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core-shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79-9.75 s(-1) mM(-1); r2 = 7.98-14.22 s(-1) mM(-1)) compared with fresh Gd(DTPA) (r1 = 4.13 s(-1) mM(-1) and r2 = 4.40 s(-1) mM(-1)), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon.
能够同时封装治疗剂、诊断剂和靶向剂的治疗诊断系统的新制备方法备受关注。这项工作首次报道了使用同轴静电纺丝制备核壳纤维形式的此类系统。用Eudragit S100形成纤维的外壳，而内核包含负载有磁共振造影剂钆（III）二乙三胺五乙酸水合物（Gd(DTPA)）和作为模型治疗剂的吲哚美辛的聚环氧乙烷。电子显微镜显示，这些纤维具有清晰核壳结构的线性圆柱形形态。X射线衍射和差示扫描量热法证明，吲哚美辛和Gd(DTPA)在纤维中均以无定形物理形式存在。这被认为是不同组分之间分子间相互作用的结果，红外光谱表明了这种相互作用的存在。体外溶出试验表明，这些纤维可通过侵蚀和扩散的联合机制实现活性成分的靶向释放。与新鲜的Gd(DTPA)（r1 = 4.13 s(-1) mM(-1)，r2 = 4.40 s(-1) mM(-1)）相比，从纤维释放到三羟甲基氨基甲烷缓冲液中的Gd(DTPA)的质子弛豫率增加（r1 = 4.79 - 9.75 s(-1) mM(-1)；r2 = 7.98 - 14.22 s(-1) mM(-1)），这证明静电纺丝并未降低该配合物的造影性能。本文报道的新系统因此为同时向结肠递送治疗剂和成像剂提供了一个新平台。
