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In this paper, we report on the fabrication of micron-sized dendrimer hydrogels (μDHs) using the water-in-oil (w/o) inverse microemulsion method coupled with the highly efficient aza -Michael addition. EDA core polyamidoamine (PAMAM) dendrimer G5 (10 w%) and polyethylene glycol diacrylate (PEG-DA, M   n  = 575 g/mol) (the molar ratio of amine/acrylate = 1/1) were dissolved in the water phase and added to hexane in the presence of surfactants span 80/tween 80 (5/1, w/w) (volume ratio of hexane to surfactants: 70:1) to form w/o microemulsions, in which PAMAM G5 cross-links with PEG-DA via the aza -Michael addition reaction. The resulting microgels are within 3-5 μm with relatively narrow size distribution. μDHs are pH-responsive degradable. They show good cytocompatibility and do not cause acute toxicity in vivo. Furthermore, they can realize a high loading of the hydrophobic drug CPT and enter the cells in the form of particles. The CPT and CPT/dendrimer complex can be slowly released following the zero-order release kinetics. Taken together, μDHs possessing hierarchically ordered dendrimers in micron domains represent a new class of microparticles with expanded structural features for programmable drug delivery and release.

macromolecules

Polyamidoamine Dendrimer Microgels: Hierarchical Arrangement of Dendrimers into Micrometer Domains with Expanded Structural Features for Programmable Drug Delivery and Release