Abstract：
Despite numerous advantages of liposomes in treating rheumatoid arthritis (RA), the in vivo stability remains a critical issue. Current strategies for improving liposomal stability often compromise their original properties. Herein, we designed an alginate nanogel-embedded liposome aiming at retaining those inherent advantages while enhancing their in vivo stability. The introduction of alginate network within the liposome core can provide mechanical support and controlled drug release without affecting the surface properties. Results showed the cross-linking of alginate network within the inner core of liposomes elevated the particle rigidity to 3 times, allowing for improved stability and decreased drug leakage. Moreover, this nanogel-embedded liposome with optimized elasticity obviously facilitated cellular uptake in inflammatory macrophages. When entering blood circulation, increased rigidity altered the composition of protein corona on the particle surface, resulting in 2-fold increase in circulation time and improved drug accumulation in arthritic joints. When anti-inflammatory chlorogenic acid (CA) was encapsulated into the nanogel network, this CA-loaded nanogel-embedded liposome significantly inhibited ROS production and inflammatory response, ultimately achieved superior therapeutic outcome in arthritic rats. Results demonstrated that this nanogel-embedded liposomes can essentially retain the inherent advantages and overcome the drawbacks of liposomes, thereby improving the drug delivery efficiency.
摘要：
尽管脂质体在治疗类风湿性关节炎（RA）方面具有许多优势，体内稳定性仍然是一个关键问题。目前用于改善脂质体稳定性的策略通常损害其原始性质。在这里，我们设计了一种藻酸盐纳米凝胶包埋脂质体，旨在保留这些固有优势，同时增强其体内稳定性。在脂质体核心内引入藻酸盐网络可以提供机械支持和受控的药物释放而不影响表面性质。结果表明，脂质体内核内的海藻酸盐网络的交联使颗粒的刚性提高到3倍，允许提高稳定性和减少药物泄漏。此外，这种具有优化弹性的纳米凝胶包埋脂质体明显促进了炎性巨噬细胞的细胞摄取.当进入血液循环时，增加的刚性改变了蛋白质日冕在颗粒表面的组成，导致循环时间增加2倍，并改善关节炎关节中的药物积累。当抗炎绿原酸（CA）被封装到纳米凝胶网络中时，这种负载CA的纳米凝胶包埋脂质体显着抑制ROS的产生和炎症反应，最终在关节炎大鼠中获得了优异的治疗效果。结果表明，这种纳米凝胶包埋的脂质体基本上保留了脂质体的固有优点，克服了脂质体的缺点，从而提高药物输送效率。
