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载铁蛋白纳米笼作为链霉素药物储库:新型药物递送系统的技术优化。

Apoferritin nanocage as streptomycin drug reservoir: Technological optimization of a new drug delivery system.

机构信息

Department of Life Sciences, Via Campi 103, University of Modena and Reggio Emilia, 41124 Modena, Italy.

CIGS, Centro Interdipartimentale Grandi Strumenti, University of Modena and Reggio Emilia, Italy.

出版信息

Int J Pharm. 2017 Feb 25;518(1-2):281-288. doi: 10.1016/j.ijpharm.2016.12.038. Epub 2016 Dec 23.

Abstract

The aim of this study is to formulate and characterize streptomycin-loaded apoferritin nanoparticles (ApoStrep NPs) for their potential therapeutic use in bacterial resistant infections (i.e. tuberculosis). ApoStrep NPs were prepared by disassembly/reassembly process via pH method and changing apoferritin/drug molar ratio, purified by dialyses process also associated with gel filtration chromatography and characterized in their chemico-physical and technological parameters as yield, size distribution, polidispersivity, morphology, internal structure, zeta potential and loading efficacy. The results showed that spherical reproducible NPs could be obtained by using apoferritin/drug molar ratio lower than 1:25 and purification based on the combination of dialysis and gel filtration chromatography. Photon correlation spectroscopy, Uv-visible detection and electron microscopy showed the maintenance of the native apoferritin chemico-physical properties and structure. When formulated with apoferritin/drug 1:10 and 1:25 molar ratio, ApoStrep NPs showed remarkable encapsulation efficacy (35% and 28%, respectively) along with kinetic profile of drug delivery, approximately 15% at 37 °C in 72h, as evidenced by "in vitro" release experiments.

摘要

本研究旨在制备并表征载链霉素脱铁铁蛋白纳米粒(ApoStrep NPs),以探索其在细菌耐药性感染(如结核病)中的潜在治疗用途。ApoStrep NPs 采用 pH 法通过解组装/再组装过程制备,并改变脱铁铁蛋白/药物的摩尔比,通过透析过程进行纯化,同时还进行凝胶过滤色谱纯化,并对其化学物理和技术参数(产率、粒径分布、多分散性、形态、内部结构、Zeta 电位和载药效率)进行了表征。结果表明,使用低于 1:25 的脱铁铁蛋白/药物摩尔比并结合透析和凝胶过滤色谱进行纯化,可以得到球形、重现性好的 NPs。光相关光谱、紫外可见检测和电子显微镜表明,脱铁铁蛋白的化学物理性质和结构得以保持。当以脱铁铁蛋白/药物 1:10 和 1:25 的摩尔比进行制剂时,ApoStrep NPs 表现出显著的包封效率(分别为 35%和 28%),并具有药物释放动力学特征,在 37°C 下 72 小时内约为 15%,这可通过“体外”释放实验证实。

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