Target delivery of drug carriers in mice kidney glomeruli via renal artery. Balance between efficiency and safety

Abstract

Targeting drug delivery systems is crucial to reducing the side effects of therapy. However, many of them are lacking effectiveness for kidney targeting, due to systemic dispersion and accumulation in the lungs and liver after intravenous administration. Renal artery administration of carriers provides their effective local accumulation but may cause irreversible vessel blockage. Therefore, the combination of the correct administration procedure, suitable drug delivery system, selection of effective and safe dosage is the key to sparing local therapy. Here, we propose the 3-μm sized fluorescent capsules based on poly-L-arginine and dextran sulfate for targeting the kidney via a mice renal artery. Hemodynamic study of the target kidney in combination with the histological analysis reveals a safe dose of microcapsules (20 × 10⁶), which has not lead to irreversible pathological changes in blood flow and kidney tissue, and provides retention of 20.5 ± 3% of the introduced capsules in the renal cortex glomeruli. Efficacy of fluorescent dye localization in the target kidney after intra-arterial administration is 9 times higher than in the opposite kidney and after intravenous injection. After 24 h microcapsules are not observed in the target kidney when the safe dose of carriers is being used but a high level of fluorescent signal persists for 48 h indicating that fluorescent cargo accumulation in tissues. Injection of non-safe microcapsule dose leads to carriers staying in glomeruli for at least 48 h which has consequences of blood flow not being restored and tissue damage being observed in histology.

Keywords: Biodistribution; Drug delivery; Kidney; Microcapsules; Renal artery injection; Safe dose.