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口服伊立替康固体脂质纳米粒偶联壳聚糖表面修饰物治疗结肠癌:制备、体外及体内评价。

Orally delivered solid lipid nanoparticles of irinotecan coupled with chitosan surface modification to treat colon cancer: Preparation, in-vitro and in-vivo evaluations.

机构信息

Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.

Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.

出版信息

Int J Biol Macromol. 2022 Jun 30;211:301-315. doi: 10.1016/j.ijbiomac.2022.05.060. Epub 2022 May 12.

Abstract

Irinotecan-loaded solid lipid nanoparticles (IRI-SLNs) was formulated and tested for its potential activity against colon cancer. IRI-SLNs were prepared by applying the principles of DoE. Nanoparticles were further surface modified using chitosan. Characterizations such as size, poly-dispersity, surface charge, morphology, entrapment, drug release pattern, cytotoxicity were conducted. In-vivo studies in male Wistar rats were carried to ascertain distribution pattern of SLNs and their acute toxicity on various vital organs. Lastly, stability of the SLNs were evaluated. Particles had a size, polydispersity and zeta potential of 430.77 ± 8.69 nm, 0.36 ± 0.02 and -40.06 ± 0.61 mV, respectively. Entrapment of IRI was 62.24 ± 2.90% in IRI-SLNs. Sustained drug release was achieved at a colonic pH and long-term stability of NPs was seen. Cytotoxicity assay results showed that SLNs exhibited toxicity on HCT-116 cells. Biodistribution studies confirmed higher concentration of drug in the colon after surface modification. An acute toxicity study conducted for 7 days showed no severe toxic effects on major organs. Thus, we picture that the developed SLNs may benefit in delivering IRI to the tumour cells, therefore decreasing the dose and dose-associated toxicities.

摘要

伊立替康负载固体脂质纳米粒(IRI-SLNs)被制备并测试其对结肠癌的潜在活性。IRL-SLNs 通过应用 DOE 的原理制备。纳米粒进一步用壳聚糖进行表面修饰。进行了诸如大小、多分散性、表面电荷、形态、包封、药物释放模式、细胞毒性等特性的表征。在雄性 Wistar 大鼠中进行了体内研究,以确定 SLNs 的分布模式及其对各种重要器官的急性毒性。最后,评估了 SLNs 的稳定性。颗粒的大小、多分散性和 Zeta 电位分别为 430.77 ± 8.69nm、0.36 ± 0.02 和-40.06 ± 0.61mV。IRL-SLNs 的包封率为 62.24 ± 2.90%。在结肠 pH 值下实现了药物的持续释放,并且观察到 NPs 的长期稳定性。细胞毒性试验结果表明,SLNs 对 HCT-116 细胞具有毒性。生物分布研究证实,表面修饰后药物在结肠中的浓度更高。为期 7 天的急性毒性研究表明,主要器官没有严重的毒性作用。因此,我们认为开发的 SLNs 可能有助于将 IRI 递送到肿瘤细胞,从而减少剂量和剂量相关的毒性。

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