Functionalized PAMAM-based Nanoformulation for Targeted Delivery of 5-Fluorouracil in Hepatocellular Carcinoma

被引：9
作者：
Chen, Siwei [1 ,2 ]
Ouyang, Hu [1 ]
He, Dongxiu [1 ,2 ]
Liu, Daquan [1 ]
Wang, Xiao [1 ]
Chen, Hongyuan [1 ]
Pan, Wei [1 ]
Li, Qi [1 ]
Xie, Weiquan [1 ]
Yu, Cuiyun [1 ,2 ]
机构：
[1] Univ South China, Inst Pharm & Pharmacol, Hengyang, Hunan, Peoples R China
[2] Univ South China, Prov Key Lab Tumor Microenvironm Respons Drug Res, 28 Western Changshen Rd, Hengyang, Hunan, Peoples R China
来源：
CURRENT PHARMACEUTICAL DESIGN | 2022年 / 28卷 / 25期
基金：
湖南省自然科学基金;
关键词：
WP05; 5-Fluorouracil; drug delivery system; functionalized PAMAM; hepatocellular carcinoma; chemotherapy; IN-VITRO; DENDRIMERS; PEPTIDE; SYSTEM; DRUGS; CELLS;
D O I：
10.2174/1381612828666220506111918
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Background: The efficacy of a traditional anticancer drug is challenged by adverse effects of the drug, including its nonspecific bio-distribution, short half-life, and side effects. Dendrimer-based targeted drug delivery system has been considered a promising strategy to increase targeting ability and reduce adverse effects of anti-cancer drugs. Objective: This study analyzed the feasibility of whether the anticancer drug 5-fluorouracil (5-FU) could be delivered by functionalized fifth-poly(amidoamine) (PAMAM) with the peptide WP05 and the acetic anhydride to the liver cancer cells, reducing the toxicity of the PAMAM and improving the targeting property of 5-FU during delivery. Methods: The functionalized PAMAM-based nanoformulation (WP05-G5.0NHAC-FUA) was fabricated through an amide condensation reaction to improve the therapeutic efficacy of 5-Fluorouracil (5-FU) in hepatocellular carcinoma (HCC). The physicochemical structure, particle size, zeta potential, stability, and in vitro release characteristics of WP05-G5.0NHAC-FUA were evaluated. In addition, the targeting, biocompatibility, anti-proliferation, and anti-migration of WP05-G5.0NHAC-FUA were investigated. The anti-tumor effect of WP05-G5.0NHAC-FUA in vivo was evaluated by constructing xenograft tumor models of human hepatoma cells (Bel-7402) implanted in nude mice. Results: The resultant WP05-G5.0NHAC-FUA displayed spherical-like nanoparticles with a size of 174.20 +/- 3.59 nm. Zeta potential and the drug loading of WP05-G5.0NHAC-FUA were 5.62 +/- 0.41mV and 28.67 +/- 1.25%, respectively. Notably, the optimized 5-FU-loaded formulation showed greater cytotoxicity with an IC50 of 30.80 +/- 4.04 mu g/mL than free 5-FU (114.93 +/- 1.43 mu g/mL) in Bel-7402 cancer liver cells, but a significantly reduced side effect relative to free 5-FU in L02 normal liver cells. In vivo animal study further confirmed efficient tumor accumulation and enhanced therapeutic efficiency. Conclusion: The developed nanoformulation is a promising platform for the targeting delivery of 5-FU and provides a promising solution for improving the efficacy of hepatocellular carcinoma chemotherapy.
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收藏
页码：2113 / 2125
页数：13
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