Polyethylene glycol (PEG) has long been used in nanoparticle-based drug or vaccine delivery platforms. In this study, nano-nicotine vaccines (NanoNicVac) were PEGylated to different degrees to investigate the impact of PEG on the immunological efficacy of the vaccine. Hybrid nanoparticles with various degrees of PEGylation (2.5%-30%) were assembled. It was found that 30% PEGylation resulted in a hybrid nanoparticle of a compromised core-shell structure. A higher concentration of PEG also led to a slower cellular uptake of hybrid nanoparticles by dendritic cells. However, increasing the quantity of the PEG could effectively reduce nanoparticle aggregation during storage and improve the stability of the hybrid nanoparticles. Subsequently, nicotine vaccines were synthesized by conjugating nicotine haptens to the differently PEGylated hybrid nanoparticles. In both in vitro and in vivo studies, it was found that a nicotine vaccine with 20% PEGylation (NanoNicVac 20.0) was significantly more stable than the vaccines with lower PEGylation. In addition, NanoNicVac 20.0 induced a significantly higher anti-nicotine antibody titer of 3.7 ± 0.6 × 104 in mice than the other NanoNicVacs with lower concentrations of PEG. In a subsequent pharmacokinetic study, the lowest brain nicotine concentration of 34 ± 11 ng/g was detected in mice that were immunized with NanoNicVac 20.0. In addition, no apparent adverse events were observed in mice immunized with NanoNicVac. In summary, 20% PEGylation confers NanoNicVac with desirable safety, the highest stability, and the best immunological efficacy in mice.

译文

聚乙二醇 (PEG) 长期以来一直用于基于纳米颗粒的药物或疫苗递送平台。在这项研究中,纳米尼古丁疫苗 (NanoNicVac) 被不同程度的聚乙二醇化,以研究PEG对疫苗免疫功效的影响。组装具有不同程度的聚乙二醇化 (2.5%-30%) 的杂化纳米颗粒。发现30% 聚乙二醇化导致核-壳结构受损的杂化纳米颗粒。较高浓度的PEG也导致树突状细胞对杂种纳米颗粒的吸收较慢。然而,增加PEG的数量可以有效地减少存储过程中纳米颗粒的聚集,并提高杂化纳米颗粒的稳定性。随后,通过将尼古丁半抗原与不同聚乙二醇化的杂化纳米颗粒结合来合成尼古丁疫苗。在体外和体内研究中,发现具有20% 聚乙二醇化的尼古丁疫苗 (NanoNicVac 20.0) 明显比具有较低聚乙二醇化的疫苗更稳定。此外,与其他浓度较低的PEG的纳米疫苗相比,纳米疫苗20.0在小鼠中诱导出3.7   ±   0.6  ×   104的抗尼古丁抗体滴度显着更高。在随后的药代动力学研究中,在用NanoNicVac 20.0免疫的小鼠中检测到最低脑尼古丁浓度为34  ±   11  ng/g。此外,在用NanoNicVac免疫的小鼠中未观察到明显的不良事件。总之,20% 聚乙二醇化赋予纳米尼伐克在小鼠中具有理想的安全性、最高的稳定性和最佳的免疫功效。

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