Shri G.H. Patel Pharmacy Building, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390 002, India.
Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, PO Box No.15, Kalabhavan, Vadodara, Gujarat, 390 001, India.
AAPS PharmSciTech. 2018 Feb;19(2):648-660. doi: 10.1208/s12249-017-0876-0. Epub 2017 Sep 25.
Darunavir has a low oral bioavailability (37%) due to its lipophilic nature, metabolism by cytochrome P450 enzymes and P-gp efflux. Lipid nanoparticles were prepared in order to overcome its low bioavailability and to increase the binding efficacy of delivery system to the lymphoid system. Darunavir-loaded lipid nanoparticles were prepared using high-pressure homogenization technique. Hydrogenated castor oil was used as lipid. Peptide, having affinity for CD4 receptors, was grafted onto the surface of nanoparticles. The nanoparticles were evaluated for various parameters. The nanoparticles showed size of less than 200 nm, zeta potential of - 35.45 mV, and a high drug entrapment efficiency (90%). 73.12% peptide was found conjugated to nanoparticles as studied using standard BSA calibration plot. Permeability of nanoparticles in Caco-2 cells was increased by 4-fold in comparison to plain drug suspension. Confocal microscopic study revealed that the nanoparticles showed higher uptake in HIV host cells (Molt-4 cells were taken as model containing CD4 receptors) as compared to non-CD4 receptor bearing Caco-2 cells. In vivo pharmacokinetic in rats showed 569% relative increase in bioavailability of darunavir as compared to plain drug suspension. The biodistribution study revealed that peptide-grafted nanoparticles showed higher uptake in various organs (also in HIV reservoir organs namely the spleen and brain) except the liver compared to non-peptide-grafted nanoparticles. The prepared nanoparticles resulted in increased binding with the HIV host cells and thus could be promising carrier in active targeting of the drugs to the HIV reservoir.
达芦那韦由于其亲脂性、细胞色素 P450 酶代谢和 P-糖蛋白外排作用，口服生物利用度低（37%）。为了克服其低生物利用度并提高递药系统与淋巴系统的结合效力，制备了载达芦那韦的脂质纳米粒。采用高压匀质技术制备达芦那韦载脂质纳米粒。氢化蓖麻油用作脂质。将具有 CD4 受体亲和力的肽接枝到纳米粒表面。对纳米粒进行了各种参数的评估。纳米粒的粒径小于 200nm，Zeta 电位为-35.45mV，药物包封效率高（90%）。通过标准 BSA 校准曲线研究，发现 73.12%的肽接枝到纳米粒上。与普通药物混悬剂相比，纳米粒在 Caco-2 细胞中的通透性增加了 4 倍。共焦显微镜研究表明，与非 CD4 受体表达的 Caco-2 细胞相比，纳米粒在含有 CD4 受体的 HIV 宿主细胞（Molt-4 细胞作为模型）中的摄取量更高。与普通药物混悬剂相比，大鼠体内药代动力学研究显示达芦那韦的生物利用度相对增加了 569%。生物分布研究表明，与非肽接枝纳米粒相比，肽接枝纳米粒在除肝脏以外的各种器官（包括 HIV 储存器官即脾和脑）中的摄取量更高。制备的纳米粒与 HIV 宿主细胞的结合增加，因此可能成为将药物主动靶向 HIV 储存库的有前途的载体。
