Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Adv Drug Deliv Rev. 2011 Sep 10;63(10-11):890-900. doi: 10.1016/j.addr.2011.05.016. Epub 2011 Jun 12.
Dendrimers are unique biomaterials that are constructed by the stepwise addition of layers (generations) of polymer around a central core. They can be constructed with a range of molecular weights and have a polyfunctional surface that facilitates the attachment of drugs and pharmacokinetic modifiers such PEG or targeting moieties. These properties have led to considerable interest in the development of dendrimers for a range of biomedical applications. After subcutaneous administration, larger dendrimers in particular (> 8 nm), preferentially drain from the injection site into the peripheral lymphatic capillaries and therefore have potential as lymphatic imaging agents for magnetic resonance and optical fluorescence lymphangiography and as vectors for drug-targeting to lymphatic sites of disease progression. In general, lymphatic targeting of dendrimers is enhanced by increasing size although ultimately larger constructs may be incompletely absorbed from the injection site. Increasing hydrophilicity and reducing surface charge enhances drainage from subcutaneous injection sites, but the reverse is true of uptake into lymph nodes where charge and hydrophobicity promote retention. Larger hydrophilic dendrimers are also capable of extravasation from the systemic circulation, absorption into the lymphatic system and recirculation into the blood. Lymphatic recirculation may therefore be a characteristic of PEGylated dendrimers with long systemic circulation times.
树突状聚合物是一种独特的生物材料，它是通过在中心核周围逐步添加聚合物层（代）来构建的。它们可以用一系列分子量来构建，并且具有多官能团表面，有利于药物和药代动力学修饰物（如 PEG 或靶向部分）的附着。这些特性使得人们对树突状聚合物在一系列生物医学应用中的开发产生了浓厚的兴趣。经皮下给药后，特别是较大的树突状聚合物（>8nm），优先从注射部位引流到外周淋巴管，因此它们具有作为磁共振和光学荧光淋巴管造影术的淋巴成像剂以及作为药物递送至疾病进展的淋巴部位的载体的潜力。一般来说，通过增加尺寸可以增强树突状聚合物的淋巴靶向性，尽管最终较大的结构可能无法从注射部位完全吸收。增加亲水性和降低表面电荷可以促进从皮下注射部位引流，但在淋巴结中则相反，电荷和疏水性促进保留。较大的亲水性树突状聚合物也能够从全身循环中逸出，被吸收到淋巴系统并重新循环到血液中。因此，淋巴再循环可能是具有长系统循环时间的聚乙二醇化树突状聚合物的特征。
