title: Synthesis of a novel polyamidoamine dendrimer conjugating with alkali blue as a lymphatic tracer and study on the lymphatic targeting in vivo.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: b Laboratory of Clinical Pharmacology , Academy of Traditional Chinese Medicine of Liaoning Province , Shenyang , PR China , and.
authors.forename: Suxia
authors.initials: S
authors.lastname: Xia
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Ye
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yao
authors.affiliation: c Department of Marketing , Henan University of Animal Husbandry and Economy , Zhengzhou , PR China.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000468:Alkalies / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D050091:Dendrimers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008751:Methylene Blue / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000468:Alkalies; D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D008751:Methylene Blue
keywords: Lymphatic drainage; lymphatic tracing; lymphatic uptake; polyamidoamin-alkali blue; subcutaneous administration