Huang Keng-Shiang, Yang Chih-Hui, Wang Ya-Chin, Wang Wei-Ting, Lu Yen-Yi
The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan.
Department of Biological Science and Technology, I-Shou University, Kaohsiung 82445, Taiwan.
Pharmaceutics. 2019 May 3;11(5):212. doi: 10.3390/pharmaceutics11050212.
Vinblastine (VBL) is a major chemotherapeutic drug; however, in some cases, it may cause severe side effects in patients with cancer. Designing a novel VBL pharmaceutical formulation is a crucial and emerging concern among researchers for reducing the use of VBL. This study developed a stimuli-responsive controlled VBL drug release system from magnetically sensitive chitosan capsules. A magnetically responsive controlled drug release system was designed by embedding superparamagnetic iron oxide (SPIO) nanoparticles (NPs) in a chitosan matrix and an external magnet. In addition, droplet microfluidics, which is a novel technique for producing polymer spheres, was used for manufacturing monodispersed chitosan microparticles. The prepared VBL and SPIO NPs-loaded chitosan microparticles were characterized and analyzed using Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, a superconducting quantum interference device, and a biocompatibility test. The drug encapsulation efficiency was 67%-69%. The in vitro drug release test indicated that the VBL could be 100% released from chitosan composite particles in 80-130 min under magnetic stimulation. The pulsatile magnetically triggered tests showed individual and distinctive controlled release patterns. Thus, the timing and dose of VBL release was controllable by an external magnet. The results presume that using a magnetically responsive controlled drug release system offers a valuable opportunity for VBL drug delivery, where the delivery system is an active participant, rather than a passive vehicle, in the optimization of cancer treatment. The proposed actively targeted magnetic drug delivery system offers many advantages over conventional drug delivery systems by improving the precision and timing of drug release, easy operation, and higher compliance for pharmaceutical applications.
长春碱（VBL）是一种主要的化疗药物；然而，在某些情况下，它可能会给癌症患者带来严重的副作用。设计一种新型的VBL药物制剂是研究人员减少VBL使用量的关键且新兴的关注点。本研究从磁敏壳聚糖胶囊开发了一种刺激响应性可控的VBL药物释放系统。通过将超顺磁性氧化铁（SPIO）纳米颗粒（NPs）嵌入壳聚糖基质并结合外部磁体，设计了一种磁响应性可控药物释放系统。此外，作为一种生产聚合物球的新技术，微流控液滴法被用于制造单分散壳聚糖微粒。使用傅里叶变换红外光谱、透射电子显微镜、扫描电子显微镜、超导量子干涉装置和生物相容性测试对制备的负载VBL和SPIO NPs的壳聚糖微粒进行了表征和分析。药物包封率为67%-69%。体外药物释放试验表明，在磁刺激下，VBL可在80-130分钟内从壳聚糖复合颗粒中100%释放。脉动磁触发试验显示出独特的可控释放模式。因此，VBL释放的时间和剂量可通过外部磁体控制。结果表明，使用磁响应性可控药物释放系统为VBL药物递送提供了一个宝贵的机会，在癌症治疗优化中，该递送系统是一个积极的参与者，而不是一个被动的载体。所提出的主动靶向磁控药物递送系统通过提高药物释放的精度和时间、易于操作以及在药物应用中具有更高的顺应性，比传统药物递送系统具有许多优势。
