| Autor: |
Yang R; a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China.; b Laboratory of Clinical Pharmacology , Academy of Traditional Chinese Medicine of Liaoning Province , Shenyang , PR China , and., Xia S; b Laboratory of Clinical Pharmacology , Academy of Traditional Chinese Medicine of Liaoning Province , Shenyang , PR China , and., Ye T; a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China., Yao J; a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China., Zhang R; c Department of Marketing , Henan University of Animal Husbandry and Economy , Zhengzhou , PR China., Wang S; a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China., Wang S; a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China. |
| Abstrakt: |
In this study, a novel lymphatic tracer polyamidoamin-alkali blue (PAMAM-AB) was synthesized in order to evaluate the intra-lymphatic targeting ability and lymphatic tropism of PAMAM-AB after subcutaneous administration. UV-Vis, FT-IR, NMR and HPLC characterization were performed to prove the successful synthesis of PAMAM-AB. The calculated AB payload of PAMAM-AB conjugate was seven per dendrimer molecule (27.16% by weight). Hydrolysis stability of PAMAM-AB in vitro was evaluated, which was stable in PBS and human plasma. Lymphatic tracing were studied to determine the blue-stained intensity of PAMAM-AB in right popliteral lymph nodes (PLNs), iliac lymph nodes (ILNs) and para-aortic lymph nodes (PALNs) after subcutaneous administration. The pharmacokinetics and biodistribution of PAMAM-AB in mice were investigated. PLNs, ILNs and PALNs could be obviously blue-stained within 10 min after PAMAM-AB administration, and displayed a more rapid lymphatic absorption, a higher AUC value in lymph nodes and a longer lymph nodes residence time compared with methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), MB multiple microemulsion (MB-MME). Enhanced lymphatic drainage from the injection site and uptake into lymph of PAMAM-AB indicated that PAMAM-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors or as a lymphatic tracer in its own right. |
