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Engineering polymeric nanocapsules for an efficient drainage and biodistribution in the lymphatic system

Abstract Polymer-based nanocarriers have shown potential for enhancing the immunological response of antigens. However, the key drivers for this response have not been fully elucidated. The objective of this work was to evaluate the influence of particle size (≈100 versus 200 nm) and surface composition of polymeric nanocapsules (chitosan, polyarginine and carboxymethyl-β-glucan) on their ability to target specific immune cells in the lymphatics. For this purpose, we used a powerful imaging technique, two-photon intravital microscopy, which minimises tissue damage in the visualisation of biological processes at cellular/subcellular levels. As expected, particle size was critical in the distribution and lymph node accumulation of all nanocapsules. Chitosan particles with a mean size below 100 nm accumulated significantly more in the popliteal lymph node than those with a larger size. Additionally, a comparative analysis of 100 nm nanocapsules with different polymeric shells indicated that cationic nanocapsules (chitosan and polyarginine) show higher accumulation in the popliteal lymph node than the anionic ones (carboxymethyl-β-glucan). In contrast, these anionic nanocapsules showed significant accumulation in the lumbar lymph node. In conclusion, tuning the physicochemical properties and composition of the nanocapsules allows the modulation of their lymphatic uptake and biodistribution, which may have important implications in the immune response.