Fate of Various Dendrimers with Different Sizes and Surfaces after Subcutaneous and Intradermal Administration

Dendrimers are synthetic macromolecules with highly controllable structures, which are potent multifunctional nanoparticles for drug delivery system and imaging. There are many reports on intravenous administration of... [ view full abstract ]

Dendrimers are synthetic macromolecules with highly controllable structures, which are potent multifunctional nanoparticles for drug delivery system and imaging. There are many reports on intravenous administration of dendrimer, but few on intradermal and subcutaneous administration. In this study, various dendrimers of different generations (G2, G4, G6, and G8) and different surfaces (amino, carboxyl, acetyl and collagen peptide modification) were prepared and radiolabeled. First, the radiolabeled dendrimers were intradermally administrated to the right footpad of rats. All G2 dendrimers were predominantly accumulated in the kidney. Amino-terminal, acetyl-terminal and carboxy-terminal dendrimers of greater than G4 were mostly located at the injection site, in blood and in the popliteal lymph node, respectively. Interestingly, the carboxy-terminal dendrimers were not largely recognized by macrophages and T cells in the lymph node. Finally, the lymph detection was performed by single photon emission computed tomography (SPECT) imaging using various dendrimers. (Figure 1). Carboxy-terminal dendrimers of greater than G4 and amino-terminal G6 dendrimer (G6-NH2) successfully visualized the popliteal lymph node (indicated by arrows), but acetyl-terminal G6 dendrimer (G6-Ac) and carboxy-terminal G2 dendrimer (G2-COOH) did not. Compared with the COOH-terminal dendrimers of higher than G4, G6-NH2 was largely retained at the injection site (indicated by arrow heads). These results suggest that carboxy-terminal dendrimers of greater than G4 are useful for drug delivery and imaging of sentinel lymph node, which the first lymph node draining tumor cells. Next, the radiolabeled dendrimers were subcutaneously administrated into tumor-bearing mice, and monitored by using SPECT imaging. Acetylated G4 dendrimer (Ac-G4) and collagen peptide-conjugated dendrimer (CP-G4) were largely retained at the injection site for at least 1 day (indicated by arrows). Ac-G4 were partly accumulated in the kidney (indicated by K), but the CP-G4 was not (Figure 2). On the other hand, these dendrimers were accumulated in the liver and the kidney following intravenous administration. These results indicate that the subcutaneously injected dendrimers did not largely gain substantial access to the systemic circulation, which is useful for a depot of drug around the injection site.