叶酸修饰的Crebanine 聚乙二醇-聚乳酸共聚物纳米粒子的药代动力学及抗肿瘤药效学初步研究
Preliminary Study on Pharmacokinetics and Antitumor Pharmacodynamics of Folic Acid Modified Crebanine Polyethyleneglycol-Polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles
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影响因子:6.5
分区:医学2区 / 药学2区 纳米科技3区
发表日期:2024
作者:
Xin Cheng, Rui Pan, Junze Tang, Kun Yu, Hailiang Zhang, Xiaoyu Zhao
DOI:
10.2147/IJN.S477027
摘要
肝癌与发病率和死亡率显著相关。低强度超声结合纳米药物传递系统在肝癌治疗中具有潜力，成为一种替代方案。本研究着重于利用叶酸（FA）修饰的纳米粒子，这些纳米粒子载有荧光染料DiR和液态氟碳（PFP），具有在超声刺激下增强肝癌靶向的潜力，并展望其在体内的应用。研究了叶酸修饰的Crebanine聚乙二醇-聚乳酸共聚物纳米粒子（FA-Cre@PEG-PLGA NPs）的药代动力学和组织分布，评估了其药代动力学参数、肝脏靶向性及体内分布情况。此外，还在体外研究了FA-Cre@PEG-PLGA NPs结合超声照射对鼠肝癌H22细胞增殖及急性毒性抑制作用。利用小动物体内成像系统和原位肝细胞癌移植模型，评估了FA-Cre@PEG-PLGA NPs的肿瘤靶向性及抗肿瘤效果。药代动力学和组织分布试验表明，FA-Cre@PEG-PLGA NPs显著延长了药物在大鼠中的半衰期和滞留时间，肝脏靶向作用明显。体内急性毒性试验显示，FA-Cre@PEG-PLGA NPs具有较少的不良反应，能够达到减轻药物毒性的目的。动物实验结果进一步证实，该纳米粒子在肿瘤部位的滞留时间更长，抗肿瘤效果更优，对肝脏和肾脏组织的损伤较少。结合超声照射的FA-Cre@PEG-PLGA NPs在体内表现出极佳的安全性和强大的抗肿瘤效果，为结合超声技术与纳米药物传递系统的肝癌治疗提供了有前景的策略。
Abstract
Liver cancer is associated significantly with morbidity and mortality. The combination of low-intensity ultrasound with nanomedicine delivery systems holds promise as an alternative for the treatment for liver cancer. This study focuses on the utilization of folic acid (FA) modified nanoparticles, which are loaded with fluorescent dye DiR and liquid fluorocarbon (PFP). These nanoparticles have the potential to enhance liver cancer targeting under ultrasound stimulation and future applications in vivo.The pharmacokinetics and tissue distribution of folic acid-modified Crebanine polyethylene glycol-polylactic acid copolymer nanoparticles (FA-Cre@PEG-PLGA NPs) were investigated. The pharmacokinetic parameters, liver targeting, and in vivo distribution were assessed. Additionally, the inhibitory impacts of FA-Cre@PEG-PLGA NPs in combination with ultrasonic irradiation on the proliferation and acute toxicity of H22 cells of mouse hepatoma were investigated in vitro. The tumor targeting and anti-tumor efficacy of FA-Cre@PEG-PLGA NPs were assessed utilizing a small animal in vivo imaging system and an in situ hepatocellular carcinoma transplantation model, respectively.The pharmacokinetic studies and tissue distribution tests demonstrated that FA-Cre@PEG-PLGA NPs conspicuously prolonged the half-life and retention time of the drug in rats, and the liver targeting effect was pronounced. Additionally, the in vivo acute toxicity test indicated that FA-Cre@PEG-PLGA NPs had minimal adverse reactions and could fulfill the aim of attenuating the drug. The outcomes of the animal experiments further substantiated that FA-Cre@PEG-PLGA NPs had a longer retention time at the tumor site, a superior anti-tumor effect, and less damage to liver and kidney tissue.The integration of FA-Cre@PEG-PLGA NPs with ultrasound irradiation demonstrated exceptional safety and potent anti-tumor efficacy in vivo, presenting a promising therapeutic strategy for the treatment of liver cancer through the combination of ultrasound technology with a nanomedicine delivery system.