Engineering single-layered poly(amidoamine) dendrimer microcapsules for enhanced cellular uptake

Microcapsules are considered as one of the most promising drug carriers due to their exceptional characteristics. The cellular uptake of microcapsules is determined by physicochemical properties, yet comprehensive studies on thickness and shape effects are limited. In this study, we developed single-layered poly(amidoamine) (PAMAM) dendrimer microcapsules with tunable thicknesses and morphologies to systematically investigate their cellular internalization. By varying PAMAM generations (G2-G8), the wall thickness can be tuned within the range of 19.3-53.7 nm, while the microcapsule shapes can be determined by the distinct morphologies of the CaCO₃ templates (spherical, peanut-like, dumbbell-like). Cellular uptake studies in DC2.4 cells revealed significant thickness- and shape-dependent trends: among spherical microcapsules, OPC/PAMAM-G6 microcapsules with a thickness of 43.5 nm exhibited higher internalization efficiency than their counterparts, while among OPC/PAMAM-G6 microcapsules, dumbbell-like microcapsules outperformed spherical and peanut-like microcapsules. Notably, dumbbell-shaped microcapsules with negative surface charge (-11.8 mV) demonstrated superior biocompatibility and uptake kinetics. This study demonstrates the structural diversity and functional versatility of PAMAM microcapsules by utilizing oligomeric proanthocyanidins (OPC), proposing a simple and universal method for preparing polyphenol/polymer microcapsules that can be applied to practical drug delivery systems.