کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5032869 | 1471147 | 2017 | 10 صفحه PDF | دانلود رایگان |
Drug conjugation to dendrimer-based delivery systems has been shown to enhance delivery to the lymphatic system after subcutaneous administration. Dendrimer interaction with components of the interstitium at the injection site, however, may prevent drainage from the injection site. The current study sought to vary the length of a linker employed to conjugate methotrexate (MTX) to a PEGylated dendrimer, in an attempt to reduce MTX interaction with interstitial binding sites and enhance lymphatic drainage. Dendrimers with shorter linkers resulted in higher lymphatic drainage, presumably via shielding of interaction sites by the PEG mantle, but were not retained in lymph nodes. Improved drainage of dendrimers with longer linkers was achieved through coadministration with dextran to mask interactions at the injection site while maintaining retention within the node. Enhanced drug exposure to the lymph node has the potential to enhance the treatment of lymph-node resident cancer metastases.
Graphical AbstractFor many cancers, the lymphatic system is the initial site of metastatic spread and a source of ongoing spread to vital organs. Chemotherapeutic treatments that preferentially target the lymphatic system are therefore required. Methotrexate-conjugated dendrimers were administered subcutaneously to rats in an effort to achieve high lymphatic concentrations of chemotherapeutic via direct drainage from the injection site. Limited lymphatic drainage of a methotrexate-dendrimer was remedied via coadministration of dextran or albumin that both improved injection site drainage of the dendrimer and substantially increased both lymphatic and systemic exposure of the chemotherapeutic-conjugate.238
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 13, Issue 8, November 2017, Pages 2485-2494