title: Study on enhanced lymphatic exposure of polyamidoamin-alkali blue dendrimer for paclitaxel delivery and influence of the osmotic pressure on the lymphatic targeting.
abstract: In this study, paclitaxel (PTX)-loaded polyamidoamin-alkali blue (PTX-P-AB) was prepared in order to investigate the intralymphatic targeting ability and anti-cancer effect after subcutaneous (s.c.) administration. The physicochemical properties and in vitro drug release were evaluated. The lymphatic drainage and lymph nodes (LNs) uptake were examined by pharmacokinetics and distribution recovery of PTX in plasma, LNs, injection site (IS) and tissues after s.c. injection in healthy mice and in tumor-bearing mice. The osmotic pressure of PTX-P-AB affecting the lymphatic targeting was studied. The anti-tumor activity of PTX-P-AB was investigated in mice bearing S180 metastatic tumors. Results showed that PTX-P-AB with suitable and stable physicochemical properties could be used for in vivo lymphatic studies, and displayed the more rapid lymphatic absorption, the higher AUC value in LNs, the longer LNs residence time and the higher metastasis-inhibiting rate compared with Taxol®. Enhanced lymphatic drainage from the IS and uptake into lymph by increasing the osmotic pressure of PTX-P-AB indicated that PTX-P-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors and the lymphatic tracer for treatment and diagnosis.
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , P.R. China and.|b Laboratory of Clinical Pharmacology, Academe of Traditional Chinese Medicine of Liaoning Province , Shenyang , P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , P.R. China and.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Mao
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , P.R. China and.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Ye
authors.affiliation: b Laboratory of Clinical Pharmacology, Academe of Traditional Chinese Medicine of Liaoning Province , Shenyang , P.R. China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Xia
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , P.R. China and.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , P.R. China and.
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D008198:Lymph Nodes / Q000737:chemistry* / Q000187:drug effects*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009997:Osmotic Pressure; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D011073:Polyamines; C000615933:polyamidoamin-alkali blue; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Lymphatic drainage and uptake; lymphatic targeting; osmotic pressure; polyamidoamin-alkali blue; subcutaneous administration