Stability of plant virus-based nanocarriers in gastrointestinal fluids.

Stability of plant virus-based nanocarriers in gastrointestinal fluids.
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DOI:
10.1039/c7nr07182e
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发表时间:
2018-01-25
期刊:
影响因子:
6.7
通讯作者:
Lomonossoff GP
Lomonossoff GP
中科院分区:
材料科学2区
文献类型:
--
作者:
Berardi A;Evans DJ;Baldelli Bombelli F;Lomonossoff GP

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胃液和肠液中的病毒纳米颗粒:消化、变性、聚集和蛋白质冠形成的评价。豇豆花叶病毒(CPMV)是一种植物病毒,其作为用于肠胃外给药的药物递送和疫苗纳米载体被广泛研究。然而,到目前为止,很少有人知道的适用性植物为基础的纳米载体口服。在本研究中,评价了CPMV及其空病毒样颗粒(eVLP)在类似于胃肠液的条件下的胶体(即聚集)、物理(即变性)和化学(即多肽的消化)稳定性。将纳米颗粒在各种模拟胃液和肠液以及猪胃液和肠液中孵育。CPMV和eVLP具有相似的稳定性。在模拟胃介质中,它们在pH ≥ 2.5时稳定。在较低的pH值下,发生颗粒结构的不稳定,这反过来又使多肽对胃蛋白酶消化极其敏感。然而,CPMV和eVLP在模拟肠液、猪胃液和猪肠液中均稳定。因此,尽管CPMV是基于蛋白质的纳米颗粒,但其对苛刻的GI条件的耐受性比可溶性蛋白质强得多。值得注意的是,在猪胃液和肠液中孵育的CPMV和eVLP均不受蛋白质吸附的影响,没有形成可检测的蛋白质冠。GI液中CPMV和eVLP表面上缺乏蛋白质冠意味着,如果口服给药,这些纳米颗粒可以保持其天然表面特征;因此,它们的生物相互作用将保持可预测性和不变。总之,CPMV和eVLP可以被认为是用于需要口服递送的应用的有前景的纳米载体,因为它们具有化学、物理和胶体稳定性,并且在大多数测试条件下缺乏来自环境的蛋白质吸附。
Viral nanoparticles in gastric and intestinal fluids: evaluation of digestion, denaturation, aggregation and protein corona formation. Cowpea mosaic virus (CPMV) is a plant virus which is being extensively investigated as a drug delivery and vaccine nanocarrier for parenteral administration. However, to date little is known about the suitability of plant-based nanocarriers for oral delivery. In this study, the colloidal (i.e. aggregation), physical (i.e. denaturation) and chemical (i.e. digestion of the polypeptides) stability of CPMV and its empty virus-like particles (eVLPs) in conditions resembling the gastrointestinal fluids were evaluated. The nanoparticles were incubated in various simulated gastric and intestinal fluids and in pig gastric and intestinal fluids. CPMV and eVLPs had similar stabilities. In simulated gastric media, they were stable at pH ≥ 2.5. At lower pH destabilisation of the particle structure occurred, which, in turn, rendered the polypeptides extremely sensitive to pepsin digestion. However, both CPMV and eVLPs were stable in simulated intestinal fluids, in pig gastric fluids and in pig intestinal fluids. Thus CPMV, despite being a protein-based nanoparticle, was much more resistant to the harsh GI conditions than soluble proteins. Remarkably, both CPMV and eVLPs incubated in pig gastric and intestinal fluids were not subject to protein adsorption, with no formation of a detectable protein corona. The lack of a protein corona on CPMV and eVLP surfaces in GI fluids would imply that, if orally administered, these nanoparticles could maintain their native surface characteristics; thus, their biological interactions would remain predictable and unchanged. In summary, CPMV and eVLPs can be considered promising nanocarriers for applications requiring oral delivery, given their chemical, physical and colloidal stability and lack of protein adsorption from the environment in most of the tested conditions.
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