Kaur Amandeep, Jain Subheet, Tiwary Ashok K
Department of Pharmaceutical Sciences, Drug Research Punjabi University, Patiala, Punjab, 147 002, India.
Acta Pharm. 2008 Mar;58(1):61-74. doi: 10.2478/v10007-007-0045-1.
Macrophages of the reticuloendothelial system and brain act as major reservoir for HIV because of their long term survival after HIV infection and ability to spread virus particles to bystander CD4 positive lymphocyte cells. The objective of the present study was to investigate mannan-coated nanoparticles for macrophage targeting of didanosine. Different didanosine loaded nanoparticles were prepared using the double desolvation technique and were characterized in vitro, ex vivo and in vivo. Results of the ex vivo cellular uptake study indicated 5-fold higher uptake of didanosine from the mannan-coated nanoparticles formulation (62.5 +/- 5.4%) by the macrophages in comparison with didanosine solution in phosphate buffer saline (PBS, pH 7.4) (12.1 +/- 2.3%). The better cellular uptake from the nanoparticles formulation was further confirmed by fluorescence microscopy using hydrophilic 6-carboxyfluorescein as a marker. Results of the quantitative biodistribution study showed 1.7, 12.6 and 12.4 times higher localization of didanosine in the spleen, lymph nodes and brain, respectively, after administration of mannan-coated nanoparticles compared to that after injection of didanosine solution in PBS (pH 7.4). Results of the present study showed that the mannan-coated nanoparticles targeted didanosine to the macrophage by mannosyl receptor mediated endocytosis.
由于巨噬细胞在感染HIV后能长期存活且有能力将病毒颗粒传播给旁观的CD4阳性淋巴细胞，因此网状内皮系统和大脑中的巨噬细胞成为HIV的主要储存库。本研究的目的是研究甘露糖包被的纳米颗粒对巨噬细胞的靶向作用，以递送去羟肌苷。采用复乳法制备了不同的载去羟肌苷纳米颗粒，并对其进行了体外、离体和体内表征。离体细胞摄取研究结果表明，与磷酸盐缓冲盐水（PBS，pH 7.4）中的去羟肌苷溶液（12.1±2.3%）相比，巨噬细胞从甘露糖包被的纳米颗粒制剂中摄取去羟肌苷的量高5倍（62.5±5.4%）。以亲水性6-羧基荧光素为标记物的荧光显微镜进一步证实了纳米颗粒制剂具有更好的细胞摄取效果。定量生物分布研究结果显示，与注射PBS（pH 7.4）中的去羟肌苷溶液相比，给予甘露糖包被的纳米颗粒后，去羟肌苷在脾脏、淋巴结和大脑中的定位分别高1.7、12.6和12.4倍。本研究结果表明，甘露糖包被的纳米颗粒通过甘露糖受体介导内吞作用将去羟肌苷靶向递送至巨噬细胞。
