Sun Hyeongdeok, Choi Daheui, Heo Jiwoong, Jung Se Yong, Hong Jinkee
Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Korea.
Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea.
Cancers (Basel). 2020 Mar 5;12(3):593. doi: 10.3390/cancers12030593.
This study demonstrates the possibility of developing a rapidly degradable chitosan-based multilayer film for controlled drug release. The chitosan (CHI)-based multilayer nanofilms were prepared with three different types of anions, hyaluronic acid (HA), alginic acid (ALG) and tannic acid (TA). Taking advantage of the Layer-by-Layer (LBL) assembly, each multilayer film has different morphology, porosity and thickness depending on their ionic density, molecular structure and the polymer functionality of the building blocks. We loaded drug models such as doxorubicin hydrochloride (DOX), fluorescein isothiocyanate (FITC) and ovalbumin (Ova) into multilayer films and analyzed the drug loading and release profiles in phosphate-buffered saline (PBS) buffer with the same osmolarity and temperature as the human body. Despite the rapid degradation of the multilayer film in a high pH and salt solution, the drug release profile can be controlled by increasing the functional group density, which results in interaction with the drug. In particular, the abundant carboxylate groups in the CHI/HA film increased the loading amount of DOX and decreased rapid drug release. The TA interaction with DOX via electrostatic interaction, hydrogen bonding and hydrophobic interaction showed a sustained drug release profile. These results serve as principles for fabricating a tailored multilayer film for drug delivery application.
本研究证明了开发一种用于控释药物的可快速降解的壳聚糖基多层膜的可能性。基于壳聚糖（CHI）的多层纳米膜是用三种不同类型的阴离子，即透明质酸（HA）、海藻酸（ALG）和单宁酸（TA）制备的。利用逐层（LBL）组装技术，每种多层膜根据其离子密度、分子结构和构建单元的聚合物功能具有不同的形态、孔隙率和厚度。我们将盐酸阿霉素（DOX）、异硫氰酸荧光素（FITC）和卵清蛋白（Ova）等药物模型载入多层膜中，并在与人体具有相同渗透压和温度的磷酸盐缓冲盐水（PBS）缓冲液中分析药物负载和释放曲线。尽管多层膜在高pH值和盐溶液中会快速降解，但通过增加官能团密度可以控制药物释放曲线，这会导致与药物发生相互作用。特别是，CHI/HA膜中丰富的羧酸盐基团增加了DOX的负载量并减少了药物的快速释放。TA与DOX通过静电相互作用、氢键和疏水相互作用表现出持续的药物释放曲线。这些结果为制备用于药物递送应用的定制多层膜提供了原理。
