In the present study, Atazanavir sulfate-loaded solid lipid nanoparticles (ATZ-SLNs) were developed and characterized for oral bioavailability enhancement and lymphatic absorption. ATZ-SLNs were formulated by emulsion-solvent evaporation technique using hydrogenated castor oil and sodium oleate. The optimized formulation had a mean particle size of 190.1 ± 2.45 nm, the zeta potential of −42.63 ± 2.46 mV and entrapment efficiency of 94.26 ± 2.12%. Transmission electron microscopy and Field emission-scanning electron microscopy morphology indicated discrete and round structures without aggregation. In-vitro drug release study showed controlled drug release of 80.36% in 12 h in simulated intestinal fluid. Cell-line study in Caco-2 cells showed increased permeability upon SLN formulation and mode of cellular uptake of SLN as clathrin and caveoli mediated endocytosis. In-vivo pharmacokinetic study in rats indicated increased oral bioavailability using ATZ-SLNs by 200% compared to suspension formulation. A lymphatic transport study revealed that SLNs were transported via lymphatic vessels. In organ biodistribution study, peyer's patch region showed a 4.5 fold higher uptake of ATZ through ATZ-SLNs formulation than non-peyer's patch region and high accumulation in spleen and brain. This delivery approach could maximize the drug concentrations to the lymphatic system leading to effective therapy for HIV.

在本研究中，开发并表征了负载阿扎那韦硫酸盐的固体脂质纳米颗粒 (ATZ-SLN)，以提高口服生物利用度和淋巴吸收。ATZ-SLNs 通过乳化溶剂蒸发技术使用氢化蓖麻油和油酸钠配制而成。优化后的配方平均粒径为 190.1 ± 2.45 nm，zeta 电位为 -42.63 ± 2.46 mV，包埋效率为 94.26 ± 2.12%。透射电子显微镜和场发射扫描电子显微镜形态表明没有聚集的离散和圆形结构。体外药物释放研究表明，在模拟肠液中，12 小时内受控药物释放率为 80.36%。Caco-2 细胞中的细胞系研究表明，SLN 制剂的渗透性增加，以及细胞摄取 SLN 的模式为网格蛋白和小窝介导的内吞作用。大鼠体内药代动力学研究表明，与悬浮剂相比，使用 ATZ-SLNs 的口服生物利用度增加了 200%。一项淋巴转运研究表明，SLN 是通过淋巴管转运的。在器官生物分布研究中，通过 ATZ-SLNs 制剂对 ATZ 的吸收比非 peyer 斑区域高 4.5 倍，并且在脾脏和大脑中的高度积累。这种递送方法可以最大限度地提高淋巴系统的药物浓度，从而有效治疗 HIV。