Biodistribution and lymph node retention of polysaccharide-based immunostimulating nanocapsules

• We studied the biodistribution of PG-nanocapsules using scintigraphic imaging.
• We report an efficient method for radiolabeling PG nanocapsules using indium-111.
• PG-nanocapsules formed a depot at the injection site compared with In-111 control.
• PG-nanocapsules were retained in draining lymph nodes for a prolonged time.
• Lymphatic distribution of PG-nanocapsules may describe reported adjuvant effects.

The adjuvant properties of polyglucosamine/squalene-based nanocapsules (PG-nanocapsules) associated with different subunit antigens has been previously reported. Thus, the aim of the present study was to monitor the biodistribution of PG-nanocapsules and their affinity for the draining lymph nodes after subcutaneous (s.c.) injection. The nanocapsules were efficiently radiolabeled with indium-111 (111In) (labeling efficiency of 98%). The diameter and zeta potential values of the unlabeled nanocapsules was preserved after the radiolabeling process and only 20% of the 111In dissociated from the nanocapsules after 48 h of incubation in serum. The radiolabeled nanocapsules and the control 111InCl3 in saline solution (18.5 MBq (500 μCi) in 100 μL) were injected s.c. in New Zealand White rabbits. The γ-scintigraphy imaging analysis revealed a slow clearance of the nanocapsules from the injection site and their progressive accumulation in the popliteal lymph node over time (3.8% ± 1.2 of the injected dose at 48 h). Indeed, the clearance rate of the nanocapsules from the injection site was significantly slower than that of the control (free 111InCl3), which rapidly drained into systemic circulation and accumulated mainly in excretion organs (i.e. kidneys and liver). In contrast, the biodistribution of nanocapsules was preferably limited to the lymphatic circulation. These results suggest that the immune potentiating effect previously observed for PG-nanocapsules is mainly due to the formation of a depot at the injection site, which was followed by a slow drainage into the lymphatic system and a prolonged retention in the lymph nodes.