使用负载5-氟尿嘧啶的表面改性聚乳酸-羟基乙酸共聚物纳米颗粒通过去唾液酸糖蛋白受体靶向肝癌。

Targeting liver cancer via ASGP receptor using 5-FU-loaded surface-modified PLGA nanoparticles.

作者信息

Dangi Ruchi, Hurkat Pooja, Jain Ankit, Shilpi Satish, Jain Ashish, Gulbake Arvind, Jain Sanjay K

机构信息

Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University , Sagar, Madhya Pradesh , India.

出版信息

J Microencapsul. 2014;31(5):479-87. doi: 10.3109/02652048.2013.879929. Epub 2014 Apr 3.

DOI:10.3109/02652048.2013.879929

PMID:24697169

Abstract

CONTEXT

Liver cancer is widespread liver malignancy in the world, for an estimated one million deaths annually.

OBJECTIVE

In present work, lactobionic acid conjugated PLGA nanoparticles (LDNPs) bearing 5-Fluorouracil (5-FU) were developed for targeted delivery to hepatocellular carcinoma.

MATERIALS AND METHODS

Lactobionic acid conjugated PLGA was used to prepare LDNPs using modified emulsion diffusion method.

RESULTS

They were characterised for particle morphology, particle size (below 150 nm), zeta potential and polydispersity index (PDI ∼0.35), entrapment efficiency (∼60.23%), and cumulative percent drug release.

DISCUSSION

LDNPs in ex-vivo cell line studies on human cancer cell line HepG2 exhibited significantly higher cytotoxicity compared to 5-FU and DNPs (unconjugated PLGA NPs) with growth inhibition 50% (GI50) of 66.7 µg/mL, 50.2 µg/mL and 35.5 µg/mL, respectively. In vivo studies exhibited higher drug concentration about 37.52 ± 0.68% in liver as compared to other organs and plasma.

CONCLUSION

Thus, LDNPs showed high drug loading, specificity, biocompatibility and efficacy in treatment of liver cancer.

摘要

背景

肝癌是全球范围内广泛存在的肝脏恶性肿瘤，估计每年导致100万人死亡。

目的

在本研究中，开发了负载5-氟尿嘧啶（5-FU）的乳糖酸共轭聚乳酸-羟基乙酸共聚物纳米粒（LDNPs）用于靶向递送至肝细胞癌。

材料与方法

采用改良乳液扩散法，用乳糖酸共轭聚乳酸-羟基乙酸共聚物制备LDNPs。

结果

对其进行了颗粒形态、粒径（低于150nm）、zeta电位和多分散指数（PDI约为0.35）、包封率（约60.23%）以及药物累积释放百分比的表征。

讨论

在人癌细胞系HepG2的体外细胞系研究中，LDNPs表现出比5-FU和DNPs（未共轭的聚乳酸-羟基乙酸共聚物纳米粒）显著更高的细胞毒性，生长抑制50%（GI50）分别为66.7μg/mL、50.2μg/mL和35.5μg/mL。体内研究显示，与其他器官和血浆相比，肝脏中的药物浓度更高，约为37.52±0.68%。