Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus). 381 Royal Pde, Parkville, VIC 3052, Australia.
J Control Release. 2009 Dec 3;140(2):108-16. doi: 10.1016/j.jconrel.2009.08.005. Epub 2009 Aug 15.
Polylysine dendrimers have potential as highly flexible, biodegradable nanoparticular carriers that may also promote lymphatic transport. The current study was undertaken to determine the impact of PEGylation on the absorption and lymphatic transport of polylysine dendrimers modified by surface derivatisation with PEG (200, 570 or 2000Da) or 4-benzene sulphonate following SC or IV dosing. PEGylation led to the PEG(200) derived dendrimer being rapidly and completely absorbed into the blood after SC administration, however only 3% of the administered dose was recovered in pooled thoracic lymph over 30h. Increasing the PEG chain length led to a systematic decrease in absorption into the blood and an enhancement of the proportion recovered in the lymphatics (up to 29% over 30h). For the PEG(570) and PEG(2000) derived dendrimers, indirect access to the lymph via equilibration across the capillary beds also appeared to play a role in lymphatic targeting after both IV and SC dosing. In contrast, the anionic benzene sulphonate-capped dendrimer was not well absorbed from the SC injection site (26% bioavailability) into either the blood or the lymph. The data suggest that PEGylated poly-L-lysine dendrimers are well absorbed from SC injection sites and that the extent of lymphatic transport may be enhanced by increasing the size of the PEGylated dendrimer complex.
聚赖氨酸树枝状聚合物具有作为高度灵活、可生物降解的纳米载体的潜力，也可能促进淋巴转运。本研究旨在确定聚乙二醇化对经表面衍生化的聚赖氨酸树枝状聚合物（用 PEG（200、570 或 2000Da）或 4-苯磺酸衍生化）的吸收和淋巴转运的影响，这些树枝状聚合物经 SC 或 IV 给药。PEG 化导致经 SC 给药后，PEG（200）衍生的树枝状聚合物迅速且完全被吸收到血液中，然而，在 30 小时内，仅 3%的给药剂量回收于胸淋巴中。增加 PEG 链长导致吸收到血液中的系统性减少，并增强了在淋巴系统中回收的比例（在 30 小时内高达 29%）。对于 PEG（570）和 PEG（2000）衍生的树枝状聚合物，通过在毛细血管床之间平衡，间接进入淋巴液也似乎在 IV 和 SC 给药后对淋巴靶向发挥作用。相比之下，阴离子苯磺酸封端的树枝状聚合物从 SC 注射部位（26%的生物利用度）进入血液或淋巴液的吸收都不好。数据表明，PEG 化聚 L-赖氨酸树枝状聚合物从 SC 注射部位吸收良好，并且通过增加 PEG 化树枝状聚合物复合物的大小，可以增强淋巴转运的程度。
