O'Mary Hannah L, Aldayel Abdulaziz M, Valdes Solange A, Naguib Youssef W, Li Xu, Salvady Karun, Cui Zhengrong
Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
Inner Mongolia Key Laboratory of Molecular Biology, Inner Mongolia Medical University , Hohhot, Inner Mongolia, China.
Mol Pharm. 2017 Jun 5;14(6):1929-1937. doi: 10.1021/acs.molpharmaceut.7b00024. Epub 2017 May 10.
Inflammation is implicated in a host of chronic illnesses. Within these inflamed tissues, the pH of the microenvironment is decreased and immune cells, particularly macrophages, infiltrate the area. Additionally, the vascular integrity of these sites is altered with increased fenestrations between endothelial cells. These distinctive properties may be exploited to enhance targeted delivery of anti-inflammatory therapies. Using a mouse model of chronic inflammation, we previously showed that acid-sensitive sheddable PEGylation increases the distribution and retention of nanoparticles in chronic inflammation sites. Here we demonstrated that surface modification of the acid-sensitive sheddable PEGylated nanoparticles with mannose, a ligand to mannose receptors present in chronic inflammation sites, significantly increases the targeted delivery of the nanoparticles to these areas. Furthermore, we showed that the acid-sensitive sheddable PEGylated, mannose-modified nanoparticles are able to significantly increase the delivery of betamethasone-21-acetate (BA), a model anti-inflammatory compound, to chronic inflammation sites as compared to free BA. These results highlight the ability to engineer formulations to target chronic inflammation sites by exploiting the microenvironment of these regions.
炎症与许多慢性疾病有关。在这些发炎的组织中，微环境的pH值降低，免疫细胞，特别是巨噬细胞浸润到该区域。此外，这些部位的血管完整性发生改变，内皮细胞之间的窗孔增加。这些独特的特性可被利用来增强抗炎疗法的靶向递送。使用慢性炎症小鼠模型，我们之前表明酸敏感可脱落聚乙二醇化增加了纳米颗粒在慢性炎症部位的分布和滞留。在这里，我们证明了用甘露糖对酸敏感可脱落聚乙二醇化纳米颗粒进行表面修饰，甘露糖是慢性炎症部位存在的甘露糖受体的配体，可显著增加纳米颗粒向这些区域的靶向递送。此外，我们表明，与游离倍他米松-21-乙酸酯（BA）相比，酸敏感可脱落聚乙二醇化、甘露糖修饰的纳米颗粒能够显著增加模型抗炎化合物BA向慢性炎症部位的递送。这些结果突出了通过利用这些区域的微环境来设计靶向慢性炎症部位制剂的能力。
