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洛伐他汀纳米粒稳定的Pickering 乳液的制备及表征。

Preparation and characterization of pickering emulsion stabilized by lovastatin nanoparticles for vaccine adjuvants.

机构信息

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.

Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing 102206, PR China.

出版信息

Int J Pharm. 2024 Mar 25;653:123901. doi: 10.1016/j.ijpharm.2024.123901. Epub 2024 Feb 16.

Abstract

While research on mevalonate inhibitors as vaccine adjuvants has made great progress to enhance the effectiveness of the vaccine, co delivery of lovastatin and antigens (OVA) remains an enormous challenge. Here, we encapsulated lovastatin into PLGA nanoparticles. PLGA loading lovastatin was further emulsified with squalene to prepare Pickering emulsion. The emulsification conditions of Pickering emulsion were optimized, and the optimal preparation conditions were obtained. After loading lovastatin and OVA, the size and zeta potential of LS-PPAS/OVA was 1043.33 nm and -22.07 mv, the adsorption rate of OVA was 63.34 %. The adsorbing of LS-PLGA nanoparticles on the surface of squalene in Pickering emulsions was demonstrated by Fluorescent confocal microscopy. After immunization, LS-PPAS enhanced the activation of dendritic cells in lymph nodes, further study found LS-PPAS not only elicited elevated levels of OVA-specific IgG and its subtypes, but also promoted the secretion of TNF-α, IFN-γ, and IL-6 in serum as a marker of cellular immunity. Importantly, LS-PPAS showed sufficient security through monitoring levels of biochemical parameters in serum and pathological observation of organ following vaccinations. LS-PPAS may act as a promising vaccine carrier to produce strong humoral and cellular immunity with acceptable safety.

摘要

虽然将甲羟戊酸抑制剂作为疫苗佐剂的研究已经取得了很大进展,以提高疫苗的效果,但将洛伐他汀和抗原(OVA)共同递送仍然是一个巨大的挑战。在这里,我们将洛伐他汀包封到 PLGA 纳米颗粒中。PLGA 负载洛伐他汀进一步与角鲨烯乳化以制备 Pickering 乳液。优化了 Pickering 乳液的乳化条件,并获得了最佳的制备条件。负载洛伐他汀和 OVA 后,LS-PPAS/OVA 的粒径和 Zeta 电位为 1043.33nm 和-22.07mv,OVA 的吸附率为 63.34%。荧光共聚焦显微镜证明了 LS-PLGA 纳米颗粒在 Pickering 乳液中角鲨烯表面的吸附。免疫后,LS-PPAS 增强了淋巴结中树突状细胞的活化,进一步的研究发现,LS-PPAS 不仅诱导了 OVA 特异性 IgG 及其亚型的水平升高,还促进了 TNF-α、IFN-γ 和 IL-6 在血清中的分泌,作为细胞免疫的标志物。重要的是,通过监测接种后血清中生化参数的水平和对器官的病理观察,LS-PPAS 表现出足够的安全性。LS-PPAS 可以作为一种有前途的疫苗载体,产生强大的体液和细胞免疫,同时具有可接受的安全性。

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