Targeted Treatment of Kidney using Intravenous and Intraarterial delivery of Whey Protein Isolate-Based Microgels

Abstract

Here we report a promising whey protein isolate (WPI)-stabilized emulsion microgels for targeted drug delivery into the kidney. Investigation of stability revealed time-dependent degradation of the microgels starting at 72 h. Cytotoxicity studies showing increased sensitivity in Hek239 and Jurkat cells. A biodegradation assay underscored the role of macrophages in the destruction process of microgel particles. The efficiency of targeting the microgels for the kidney was assessed by biodistribution using intravenous and intraarterial delivery. Tail vein administration demonstrated long-term (minimum 5 days) selective accumulation not only in the liver but also in the kidneys. Renal artery injection of microgels resulted in an expected local increase in fluorescence in the target kidney in the first minutes after injection. In contrast, at 1 and 3 h there was an atypical accumulation of the Cy7 fluorescent signal in the opposite kidney. However, at 1 and 5 d the fluorescent signal predominated in the target kidney again and was higher in comparison with intravenous administration. Histological analysis validated the safety of WPI-based microgels using different methods of administration. By fine-tuning the physicochemical properties and delivery methods, the developed microgels offer an adjusted therapeutic approach with reduced side effects. They present new prospects for the treatment of kidney disorders using both intravenous administration and minimally invasive endovascular approach.