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通过明胶和普朗尼克F127的温度辅助共组装制备尺寸选择性纳米复合材料用于阿霉素的被动靶向

Preparation of a size selective nanocomposite through temperature assisted co-assembly of gelatin and pluronic F127 for passive targeting of doxorubicin.

作者信息

Das Ram Pada, Singh Beena Gobind, Kunwar Amit

机构信息

Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India.

出版信息

Biomater Sci. 2020 Aug 7;8(15):4251-4265. doi: 10.1039/d0bm00725k. Epub 2020 Jun 25.

Abstract

The preparation of a water dispersible and pH responsive gelatin-F127 nanocomposite using a thermal relaxation approach is reported. The results indicated that physical properties (size and surface charge) of the gelatin-F127 nanoparticle can be tuned by varying the F127 to gelatin weight ratio. The heating (60 °C) of a saline solution (pH 7.4) containing 0.5% (w/v) of gelatin and 20% (w/w of gelatin) of F127 followed by gradual cooling at room temperature yielded nanoparticles of desired size (160 ± 40 nm), viscosity (1.36 ± cP) and surface charge (-6.47 ± 0.7 mV). The drug delivery application of nanocarriers was investigated using doxorubicin hydrochloride (Dox) as a model drug. These nanocarriers showed high encapsulation efficiency of Dox (85%), a sustained release profile, and substantial cellular internalization. Additionally, Dox loaded nanocarriers (G-Dox) exhibited prolonged residence in blood as evidenced by their longer circulation time as compared to plain Dox. Moreover, G-Dox exhibited a higher availability of the drug in plasma as compared to nonspecific organs such as the heart, liver and kidneys, highlighting its significance in reducing drug associated side effects. Finally, the enhanced toxicity of G-Dox to a WEHI-164 (fibrosarcoma) tumor model as compared to that of plain Dox under an identical dosage of 6 mg per kg body weight (IP) confirmed its potential for chemotherapy application.

摘要

报道了一种采用热弛豫方法制备水分散性和pH响应性明胶-F127纳米复合材料的方法。结果表明,通过改变F127与明胶的重量比,可以调节明胶-F127纳米颗粒的物理性质(尺寸和表面电荷)。将含有0.5%(w/v)明胶和20%(相对于明胶的w/w)F127的盐溶液(pH 7.4)加热至60°C,然后在室温下逐渐冷却,得到了尺寸为(160±40 nm)、粘度为(1.36±cP)和表面电荷为(-6.47±0.7 mV)的理想纳米颗粒。以盐酸阿霉素(Dox)作为模型药物研究了纳米载体的药物递送应用。这些纳米载体显示出对Dox的高包封效率(85%)、缓释特性和大量的细胞内化。此外,与普通Dox相比,载有Dox的纳米载体(G-Dox)的循环时间更长,这证明它们在血液中的滞留时间延长。而且,与心脏、肝脏和肾脏等非特异性器官相比,G-Dox在血浆中的药物利用率更高,这突出了其在减少药物相关副作用方面的重要性。最后,在每千克体重6 mg(腹腔注射)的相同剂量下,与普通Dox相比,G-Dox对WEHI-164(纤维肉瘤)肿瘤模型的毒性增强,证实了其在化疗应用中的潜力。

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