An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect

A platform capable of specifically delivering an antiviral drug to the liver infected with hepatitis B is a major concern in hepatology. Vaccination has had a major effect on decreasing the emerging numbers of new cases of infection. However, the total elimination of the hepatitis B virus from the body requires prolonged therapy. In this work, we aimed to target the liver macrophages with lipid polymer hybrid nanoparticles (LPH), combining the merit of polymeric nanoparticles and lipid vesicles. The hydrophilic antiviral drug, entecavir (E), loaded LPH nanoparticles were optimized and physicochemically characterized. A modulated lipidic corona, as well as, an additional coat with vitamin E were used to extend the drug release enhance the macrophage uptake. The selected vitamin E coated LPH nanoparticles enriched with lecithin-glyceryl monostearate lipid shell exhibited high entrapment for E (80.47%), a size ≤ 200 nm for liver passive targeting, extended release over one week, proven serum stability, retained stability after refrigeration storage for 6 months. Upon macrophage uptake in vitro assessment, the presented formulation displayed promising traits, enhancing the cellular retention in J774 macrophages cells. In vivo and antiviral activity futuristic studies would help in the potential application of the ELPH in hepatitis B control.

能够将抗病毒药物精准递送至乙型肝炎病毒感染肝脏的递送平台，是肝病学领域的核心研究关切。疫苗接种在降低乙型肝炎新增感染病例数方面已取得显著成效，但彻底清除体内乙型肝炎病毒仍需长期治疗。本研究旨在借助兼具聚合物纳米粒与脂质囊泡双重优势的脂质聚合物杂合纳米粒（lipid polymer hybrid nanoparticles, LPH）实现肝脏巨噬细胞靶向递送。本研究对负载亲水性抗病毒药物恩替卡韦（entecavir, E）的LPH纳米粒进行了处方优化与理化表征。通过构建可调谐脂质冠层并额外修饰维生素E涂层，可延长药物释放周期并提升巨噬细胞摄取效率。所优选的经维生素E修饰、以卵磷脂-单硬脂酸甘油酯为脂质壳层的LPH纳米粒，展现出高达80.47%的恩替卡韦包封率，粒径≤200 nm以满足肝脏被动靶向需求，药物释放周期长达一周以上，具备良好的血清稳定性，且经6个月冷藏储存后仍可保持结构稳定。体外巨噬细胞摄取实验结果表明，该制剂表现出良好的应用潜力，可显著提升其在J774巨噬细胞中的细胞滞留能力。后续体内实验与抗病毒活性前瞻性研究，将为ELPH（负载恩替卡韦的脂质聚合物杂合纳米粒）在乙型肝炎防控中的潜在应用提供有力支撑。