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透明质酸/阿霉素纳米组装体释药微球用于肝肿瘤经动脉化疗栓塞术。

Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor.

机构信息

a College of Pharmacy , Kangwon National University , Chuncheon , Gangwon , Republic of Korea.

b Department of Radiology , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , Republic of Korea.

出版信息

Drug Deliv. 2018 Nov;25(1):1472-1483. doi: 10.1080/10717544.2018.1480673.

DOI:10.1080/10717544.2018.1480673
PMID:29909706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6058484/
Abstract

Doxorubicin (DOX)-loaded, hyaluronic acid-ceramide (HACE) nanoassembly-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were developed for transarterial chemoembolization (TACE) therapy of liver cancer. DOX/HACE MSs with a mean diameter of 27 μm and a spherical shape were prepared based on the modified emulsification method. Their in vitro biodegradability in artificial biological fluids was observed. A more sustained drug release pattern was observed from DOX/HACE MS than from DOX MS at pH 7.4. The cellular internalization efficiency of DOX of the DOX/HACE MS group was higher than that of the DOX MS group in liver cancer cells (HepG2 and McA-RH7777 cells), mainly due to CD44 receptor-mediated endocytosis of the released DOX/HACE nanoassembly. In both HepG2 and McA-RH7777 cells, the antiproliferation and apoptotic potentials of the DOX/HACE MS were significantly higher than those of the DOX MS (p < .05). Notably, in the McA-RH7777 tumor-implanted rat models, a better tumor growth suppression, a lower tumor viable portion, and a higher incidence of apoptosis were presented in the DOX/HACE MS group than in the DOX MS group after intra-arterial (IA) administration. DOX/HACE-based nanoassembly release from the DOX/HACE MS seems to elevate the cellular accumulation of DOX and its anticancer activities. The developed DOX/HACE MS can be used as a drug-loaded HA nanoassembly-releasing MS system for TACE therapy of liver cancer.

摘要

载多柔比星（DOX）、透明质酸-神经酰胺（HACE）纳米组装体的聚乳酸-共-羟基乙酸（PLGA）微球（MS）被开发用于肝癌的经动脉化疗栓塞（TACE）治疗。基于改良乳化法制备了平均直径为 27μm 且呈球形的 DOX/HACE MS。观察了它们在人工生物流体中的体外生物降解性。在 pH 7.4 时，DOX/HACE MS 比 DOX MS 具有更持续的药物释放模式。DOX/HACE MS 组的肝癌细胞（HepG2 和 McA-RH7777 细胞）中 DOX 的细胞内化效率高于 DOX MS 组，主要归因于释放的 DOX/HACE 纳米组装体的 CD44 受体介导的内吞作用。在 HepG2 和 McA-RH7777 细胞中，DOX/HACE MS 的增殖抑制和凋亡潜力均明显高于 DOX MS（p<.05）。值得注意的是，在 McA-RH7777 肿瘤植入大鼠模型中，与 DOX MS 组相比，经动脉内（IA）给药后，DOX/HACE MS 组的肿瘤生长抑制更好，肿瘤存活部分更低，凋亡发生率更高。DOX/HACE 基纳米组装体从 DOX/HACE MS 中的释放似乎提高了 DOX 的细胞蓄积及其抗癌活性。所开发的 DOX/HACE MS 可用作用于肝癌 TACE 治疗的载药 HA 纳米组装体释放 MS 系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/fcd93e1693d9/IDRD_A_1480673_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/72e6fcf813a2/IDRD_A_1480673_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/6d956531e58b/IDRD_A_1480673_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/3bbb2b833e3e/IDRD_A_1480673_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/f6f195785904/IDRD_A_1480673_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/861a27b83d76/IDRD_A_1480673_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/fcd93e1693d9/IDRD_A_1480673_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/72e6fcf813a2/IDRD_A_1480673_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/6d956531e58b/IDRD_A_1480673_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/3bbb2b833e3e/IDRD_A_1480673_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/f6f195785904/IDRD_A_1480673_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/861a27b83d76/IDRD_A_1480673_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e47e/6058484/fcd93e1693d9/IDRD_A_1480673_F0006_C.jpg

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