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 Õ . 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. KeywordsLymphatic drainage and uptake, lymphatic targeting, polyamidoamin-alkali blue, osmotic pressure, subcutaneous administration History

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

“…Lymphatic absorption is rapid, and compared to methylene blue solution, water-inoil microemulsion, and multiple microemulsion, PANAM-AB had increased lymph node AUC and longer lymphatic retention times. In another study, paclitaxel was loaded onto PANAM-AB dendrimers (PTX-P-AB) [164]. There was more absorption into the lymphatics compared to standard Taxol ® , as well as increased AUC values in the lymphatics, longer retention in lymph nodes, and increased metastasis inhibition.…”

Synthesis and Evaluation of 177Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells

“…The relatively slow PTX-releasing rate observed in vitro could be enhanced by the in vivo high oncotic pressure in tumors, since previous reports have demonstrated that the PTX release from dendrimeric systems gradually speeds up with the osmotic pressure [27].…”

Dendrimers as Nanocarriers for the Delivery of Drugs Obtained from Natural Products

“…α-tocopheryl succinate (α-TOS) (6) can increase the targeting of PTX-PAMAM dendrimers [31]. Biotin (7), omega-3 fatty acid, alkali blue, and octa-arginine (R8) (8) can also be applied to increase the targeting of PTX-loaded PAMAM, subsequently enhancing the potential for cell uptake, cytotoxicity, and apoptosis [32][33][34][35][36].…”