Development of a new polymeric formulation of rutin by supercritical antisolvent precipitation and evaluation of its nephroprotective capacity against cisplatin nephrotoxicity in rats

Nephrotoxicity associated with antitumor drugs such as cisplatin is a well-documented clinical challenge. The intrinsic toxicity of these drugs is driving the search for renoprotective strategies. Currently, one of the most popular is the use of natural substances with antioxidant properties, such as flavonoids. Rutin is a member of this family whose nephroprotective properties have already been studied. However, its bioavailability is very low due to its high lipophilicity. Polymeric nanoparticle design is one of the possible strategies used to solve pharmacokinetic problems. The aim of this work was to design and develop a new polymeric formulation of rutin and to evaluate its nephroprotective capacity against cisplatin toxicity in an experimental rat model. Rutin was processed and coated with Eudragit® polymers using the Supercritical Anti Solvent (SAS) process. A successful micronization and coating of rutin was achieved. In vitro release studies of the formulations obtained demonstrated that pure SAS-processed rutin showed a higher solubility and dissolution rate that unprocessed rutin, and that rutin coated with Eudragit® polymers combined this increased solubilization with a controlled release. However, after administration of the formulation with the best in vivo properties obtained in rats, they did not show a significant nephroprotective capacity. The histological study confirmed the negative results obtained in the functional study. Although this formulation did not show significant nephroprotective effects in vivo , the study provides valuable insights into the limitations of current polymeric encapsulation strategies for rutin. • Rutin was sucessfully encapsulated in Eudragit polymers by SAS technique • Formulations were in-vitro/in-vivo tested against cancer-therapy nephrotoxicity • Formulations showed enhanced in-vitro dissolution profiles • A limited therapeutic efficiency was observed probably due to low in vivo stability