Abstract:Background and Objectives: This study covers the biophysical aspects of the use of emulsion microgels stabilized with whey protein isolate (WPI) for targeted drug delivery to the urinary system. Emulsion microgels were prepared by the ultrasonic homogenization method which leads to denaturation of the WPI adsorbed on the water-oil interface and formation of WPI microgel layer at the oil droplet. Materials and Methods: The study of the release profile of the model substance Cyanine 7 immobilized in emulsion microgels has demonstrated a prolonged pattern over 72 hours. The effect of emulsion microgels on the viability of various cell cultures (normal fibroblasts (L929), kidney cells (Hek239), renal carcinoma (Renca) and bladder carcinoma (T24)) has been studied, which has shown a dependence of the cytotoxicity level on the cell type. The Hek239 cells have demonstrated particularly increased sensitivity to emulsion microgels. Results: The accumulation and distribution behaviour of emulsion microgels in laboratory mice have also been studied depending on the route of their administration: intravesical or intravenous. The efficiency of targeting the microgels for urinary system components of the urinary system (kidney or bladder) has been assessed by biodistribution using in vivo fluorescence imaging. Systemic administration has demonstrated selective accumulation not only in the liver but also in the kidneys. Intravesical administration has made it possible to maintain a high local concentration of Cyanine 7 in the bladder at least during 2 h. Histological analysis has validated the safety of WPI-based microgels for delivery into the bladder and kidney. Conclusions: The presented delivery system based on the developed emulsion microgels opens up new prospects for the treatment of diseases of the urinary system using both systemic administration and minimally invasive intravesical instillations.
Keywords:intravesical instillation, urinary system, whey protein isolate, drug delivery systems, emulsion microgels.