Abstract：
The present research looked for ways to develop shielded nanoparticles (NPs)-drug transporters made of chitosan (CS) to enhance the bioavailability of edoxaban tosylate monohydrate (ETM) for oral administration by examining the correlation among design aspects and data from experiments using response surface methodology (RSM). ETM-loaded CS nanoparticles (ETM-CS-NPs) were developed using the ionic gelation of CS with tripolyphosphate (TPP). Utilising Zeta-sizer and scanning electron microscopy, the ETM-CS-NPs were evaluated for particle size (PS), zeta potential (ZP), surface morphology, polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Drug and polymer interactions in NPs were assessed using Fourier transform infra-red spectroscopy. The response surface approach and Design-Expert software optimised the ETM-CS-NPs. Using RSM, the effects of independent variables such as the amount of CS, the amount of TPP, and the amount of glacial acetic acid on PS, PDI and ZP were analysed. The optimal combination of PS (354.8 nm), PDI (0.509), ZP (43.7 + mV), % EE (70.3 ± 1.3) and % DL (9.1 ± 0.4) has been identified for the optimised ETM-CS-NPs. ETM-CS-NPs\' anticoagulant activity was evaluated using activated partial thromboplastin time (aPTT), prothrombin time (PT) and thrombin time (TT) assays. In conclusion, a practical and consistent method has been established, and its application has been proven in vitro, indicating its utility for future studies of the biological distribution of ETM-CS-NPs in vivo for specific antithrombotic treatments.
摘要：
本研究通过研究设计方面与实验数据之间的相关性，寻找开发由壳聚糖（CS）制成的屏蔽纳米颗粒（NPs）-药物转运蛋白的方法，以提高口服给药依多沙班一水合物（ETM）的生物利用度。使用CS与三聚磷酸盐（TPP）的离子胶凝作用开发了负载ETM的CS纳米颗粒（ETM-CS-NP）。利用Zeta-sizer和扫描电子显微镜，评估ETM-CS-NP的粒径(PS)，zeta电位(ZP),表面形态,多分散指数(PDI)，包封效率(EE)，和载药量（DL）。使用傅里叶变换红外光谱法评估NP中的药物和聚合物相互作用。响应面方法和Design-Expert软件优化了ETM-CS-NP。使用响应面方法，自变量的影响，如CS的数量，TPP的数量，和PS上冰醋酸的含量，PDI,和ZP进行了分析。PS的最佳组合（354.8nm），PDI(0.509),ZP(43.7+mV),%EE(70.3±1.3)，和%DL(9.1±0.4)已被确定为优化的ETM-CS-NP。使用活化部分凝血活酶时间(aPTT)评估ETM-CS-NP的抗凝活性,凝血酶原时间（PT），和凝血酶时间(TT)测定。总之,建立了一种实用和一致的方法，它的应用已经在体外得到了证明，表明其在未来研究体内ETM-CS-NP的生物分布，用于特定的抗血栓治疗。
