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用于药物递送的可生物降解纳米颗粒:纳米颗粒数量对细胞毒性有影响。

Biodegradable nanoparticles designed for drug delivery: The number of nanoparticles impacts on cytotoxicity.

作者信息

Mendes Lívia Palmerston, Delgado Jorge Miguel Ferreira, Costa Angela Daniela A, Vieira Marcelo Sousa, Benfica Poliana Lopes, Lima Eliana Martins, Valadares Marize Campos

机构信息

Laboratory of Pharmaceutical Nanotechnology and Drug Delivery Systems, School of Pharmacy, Federal University of Goiás, Goiânia, Goiás, Brazil.

Escola Superior de Tecnologia e Gestão, Instituto Politécnico de Bragança, Bragança, Portugal.

出版信息

Toxicol In Vitro. 2015 Sep;29(6):1268-74. doi: 10.1016/j.tiv.2014.12.021. Epub 2015 Jan 13.

Abstract

Nanostructured drug delivery systems are based on biocompatible and biodegradable components. Composition, size and membrane surface properties are characteristics that may influence cell viability in cytotoxicity assays. In this work, four nanostructured systems commonly used for drug delivery were prepared and cytotoxicity was evaluated on human lymphocytes and Balb/c 3T3 fibroblasts. The hemolytic potential was also investigated. Polymeric nanocapsules (NC) and nanospheres (NS), nanostructured lipid carriers (NLC) and liposomes were prepared and characterized for size, distribution, zeta potential and number per volume of the colloidal dispersion. Cell viability was evaluated, 24 and 48h, by MTT and neutral red assays (NR). Cells were incubated with each particle in eight different dilutions varying from 2.1×10(4) to 2.1×10(11)particles/mL. Diameter of nanoparticles was between 130 and 200nm, all samples exhibited narrow size distribution (polydispersity index below 0.1) and zeta potential varied from -6.8 to -19.5mV. NC, NS and NLC reduced cell viability in a dilution dependent manner. For these nanoparticles, the higher number of particles induced cell death for both cell types. Liposomes did not cause loss of cell viability even at the highest number of particles. Results suggest that, depending on the kind of nanoparticle, the number of particles in the dispersion can negatively influence cell viability in pre-clinical drug development.

摘要

纳米结构药物递送系统基于生物相容性和可生物降解的成分。组成、大小和膜表面性质是可能在细胞毒性测定中影响细胞活力的特征。在这项工作中,制备了四种常用于药物递送的纳米结构系统,并评估了它们对人淋巴细胞和Balb/c 3T3成纤维细胞的细胞毒性。还研究了溶血潜力。制备了聚合物纳米胶囊(NC)、纳米球(NS)、纳米结构脂质载体(NLC)和脂质体,并对其大小、分布、zeta电位和胶体分散体每体积的数量进行了表征。通过MTT和中性红测定法(NR)在24小时和48小时评估细胞活力。将细胞与每种颗粒以八种不同的稀释度(从2.1×10⁴到2.1×10¹¹颗粒/毫升)一起孵育。纳米颗粒的直径在130至200纳米之间,所有样品均表现出窄的大小分布(多分散指数低于0.1),zeta电位在-6.8至-19.5毫伏之间变化。NC、NS和NLC以稀释依赖性方式降低细胞活力。对于这些纳米颗粒,较高数量的颗粒会导致两种细胞类型的细胞死亡。即使在最高颗粒数量下,脂质体也不会导致细胞活力丧失。结果表明,在临床前药物开发中,根据纳米颗粒的种类,分散体中颗粒的数量可能会对细胞活力产生负面影响。

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