阿霉素
壳聚糖
涂层
化疗
材料科学
聚己内酯
结合
控制释放
药品
基质(水族馆)
生物医学工程
药理学
化学
纳米技术
医学
外科
聚合物
生物化学
复合材料
生物
数学分析
生态学
数学
作者
Amina A. Voznyuk,Yulia A. Makarets,Darya Yu. Advakhova,K. Khafizov,Maksim E. Lugovoi,В. А. Захарова,Ф.С. Сенатов,Elizaveta V. Koudan
出处
期刊:ACS applied bio materials
[American Chemical Society]
日期:2024-03-13
卷期号:7 (4): 2472-2487
标识
DOI:10.1021/acsabm.4c00078
摘要
Local recurrence after surgical and therapeutic treatment remains a significant clinical problem in oncology. Recurrence may be due to imperfections in existing therapies, particularly chemotherapy. To improve antitumor activity and prevent local cancer recurrence while keeping toxicity at acceptable levels, we have developed and demonstrated a biodegradable local chemotherapy platform that provides controlled and prolonged drug release. The platform consists of a polycaprolactone (PCL) substrate, which provides the structural integrity of the platform and the predominant unidirectional drug release, and a thin multilayer coating (∼200 nm) containing doxorubicin (DOX). The coating is an electrostatic complex obtained by the layer-by-layer (LbL) assembly and consists of natural polyelectrolytes [poly-γ-glutamic acid (γ-PGA) and chitosan (CS) or poly-l-lysine (PLL)]. To improve the release stability, an ionic conjugate of DOX and γ-PGA was prepared and incorporated into the multilayer coating. By varying the structure of the coating by adding empty (without DOX) bilayers, we were able to control the kinetics of drug release. The resulting platforms contained equal numbers of empty bilayers and DOX-loaded bilayers (15 + 15 or 30 + 30 bilayers) with a maximum loading of 566 ng/cm2. The platforms demonstrated prolonged and fairly uniform drug release for more than 5 months while retaining antitumor activity in vitro on ovarian cancer cells (SKOV-3). The empty platforms (without DOX) showed good cytocompatibility and no cytotoxicity to human fibroblasts and SKOV-3 cells. This study presents the development of a local chemotherapy platform consisting of a PCL-based substrate which provides structural stability and a biodegradable polyelectrolyte layered coating which combines layers containing a polyanion ionic complex with DOX with empty bilayers to ensure prolonged and controlled drug release. Our results may provide a basis for improving the efficacy of chemotherapy using drug delivery systems.
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