Abstract：
Lipid vesicles are widely used for drug and gene delivery, but their structural instability reduces in vivo efficacy and requires specialized handling. To address these limitations, strategies like lipid cross-linking and polymer-lipid conjugation are suggested to enhance stability and biological efficacy. However, the in vivo metabolism of these altered lipids remains unclear, necessitating further studies. A new stabilization technique without chemical modification is urgently needed. Here, a bio-mimetic approach for fabricating robust multilamellar lipid vesicles to enhance in vivo delivery and stabilization of protein antigens is presented. This method leverages 1-O-acylceramide, a natural skin lipid, to facilitate the self-assembly of lipid nanovesicles. Incorporating 1-O-acylceramide, anchoring lipid bilayers akin to its role in the stratum corneum, provides excellent stability under environmental stresses, including freeze-thaw cycles. Encapsulating ovalbumin as a model antigen and the adjuvant monophosphoryl lipid A demonstrates the vesicle\'s potential as a nanovaccine platform. In vitro studies show enhanced immune responses with both unilamellar and multilamellar vesicles, but in vivo analyses highlight the superior efficiency of multilamellar vesicles in inducing higher antibody and cytokine levels. This work suggests ceramide-induced multilamellar lipid vesicles as an effective nanovaccine platform for enhanced antigen delivery and stability.
摘要：
脂质囊泡已广泛用于药物和基因递送，但它们的结构不稳定性降低了体内功效，需要专门处理运输和储存。为了解决这些限制，已经提出了诸如脂质交联和聚合物-脂质缀合的策略来增强囊泡稳定性并改善生物学功效。然而,体内代谢的化学变化的脂质仍不清楚，促使需要对其实际应用进行广泛的研究。因此，迫切需要一种无需化学改性的新稳定技术。这里,我们提出了一种生物模拟方法来制造强大的多层脂质囊泡，这大大增强了蛋白质抗原的体内递送和稳定性。我们的新方法利用1-O-酰基神经酰胺，天然存在于皮肤中的脂质，以促进脂质纳米囊泡的自组装。掺入1-O-酰基神经酰胺，锚定脂质双层的作用类似于它在角质层中的作用，在环境压力下赋予多层囊泡优异的稳定性，包括反复的冻融循环。卵清蛋白作为模型抗原和佐剂单磷酰脂质A的封装证明了杂合囊泡作为纳米疫苗平台的潜力。体外细胞研究表明，单层和多层囊泡都能增强免疫反应，但是在体内分析中，多层囊泡在诱导更高水平的抗体和细胞因子分泌方面明显更有效。这项工作表明神经酰胺诱导的多层脂质囊泡作为有效的纳米疫苗平台，有希望的增强抗原递送和稳定性，以改善体内抗原交叉呈递。本文受版权保护。保留所有权利。
