Double-Walled Microparticles-Embedded Self-Cross-Linked, Injectable, and Antibacterial Hydrogel for Controlled and Sustained Release of Chemotherapeutic Agents
Double-Walled Microparticles-Embedded Self-Cross-Linked, Injectable, and Antibacterial Hydrogel for Controlled and Sustained Release of Chemotherapeutic Agents
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DOI：
10.1021/acsami.6b03041
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发表时间：
2016-09-07
影响因子：
9.5
通讯作者：
Wang, Chi-Hwa
中科院分区：
文献类型：
--
作者：
Davoodi, Pooya;Ng, Wei Cheng;Wang, Chi-Hwa
多年来，一线癌症化疗一直是为癌症患者开的处方。然而，常规化疗在短时间内提供高剂量的非肠外抗癌药物，这可能对健康组织造成严重的毒性和有害的副作用。该研究旨在开发一种由双壁微颗粒和可注射水凝胶组成的新型给药系统（DDS），用于肿瘤局部双药给药。采用同轴电流体动力雾化（CEHDA）技术制备了负载顺铂（Cis-DDP）和紫杉醇（PTX）的均匀双壁微颗粒，并将其包埋于可注射的海藻酸支化聚乙烯亚胺中。研究结果显示了CEHDA技术的独特性，它可以简单地交换药物的位置来实现平行或顺序释放。本研究还介绍了利用计算流体动力学（CFD）对CEHDA技术的模拟，这将有助于在大规模生产微粒之前优化CEHDA的操作条件。新的合成水凝胶为Cis-DDP提供了额外的扩散屏障，并限制了药物的过早释放。此外，由于其固有的抗菌特性，水凝胶可以提供一种多功能工具，在减体积手术后的注射过程中保留肿瘤切除腔中的颗粒，并防止手术部位感染。三维MDA-MB-231（乳腺癌）球体研究表明，与免费药物治疗相比，从拟议的复合制剂中释放的药物在较长时间内具有优越的疗效和更大的球体生长减少。总之，嵌入可注射水凝胶中的新型核壳微粒可以作为灵活的控释平台，调节抗癌药物的释放谱，从而提供优越的抗癌反应。
First-line cancer chemotherapy has been prescribed for patients suffered from cancers for many years. However, conventional chemotherapy provides a high parenteral dosage of anticancer drugs over a short period, which may cause serious toxicities and detrimental side effects in healthy tissues. Tins study aims to develop a new drug delivery system (DDS) composed of double-walled micro particles and an injectable hydrogel for localized dual-agent drug delivery to tumors. The uniform double-walled micro particles loaded with cisplatin (Cis-DDP) and paclitaxel (PTX) were fabricated via coaxial electrohydrodynamic atomization (CEHDA) technique and subsequently were embedded into injectable alginate-branched polyethylenimine. The findings show the uniqueness of CEHDA technique for simply swapping the place of drugs to achieve a parallel or a sequential release profile. This study also presents the simulation of CEHDA technique using computational fluid dynamics (CFD) that will help in the optimization of CEHDA's Operating conditions prior to large-scale production of microparticles. The new synthetic hydrogel provides an additional diffusion barrier against Cis-DDP and confines premature release of drugs. In addition, the hydrogel can provide a versatile tool for retaining particles in the tumor resected cavity during the injection after debulking surgery and preventing surgical site infection due to its inherent antibacterial properties. Three-dimensional MDA-MB-231 (breast cancer) spheroid studies demonstrate a superior efficacy and a greater reduction in spheroid growth for drugs released from the proposed composite formulation over a prolonged period, as compared with free drug treatment. Overall, the new core shell microparticles embedded into injectable hydrogel can serve as a flexible controlled release platform for modulating the release profiles of anticancer drugs and subsequently providing a superior anticancer response.