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Rutin loaded bilosomes for enhancing the oral activity and nephroprotective effects of rutin in potassium dichromate induced acute nephrotoxicity in rats

A. Mohsen,Marwa Anwar Wagdi,Abeer Salama

Published 2024 in Scientific Reports

ABSTRACT

Rutin, a flavone glycoside, has shown to have a significant beneficial kidney protection effect in drug-induced nephropathy. However, its poor solubility and low oral bioavailability have limited its pharmacological applications. This study aimed at formulating rutin-loaded bilosomes to enhance the renal protective effect of rutin for oral application. Rutin-loaded bilosomes were developed using thin-film hydration technique. The prepared formulations were characterized by entrapment efficiency percentage (EE%), vesicular size (VS) and zeta potential (ZP) measurement. The developed formula exhibited moderate EE%, ranging from 20.02 ± 2.85 to 48.57 ± 3.57%, suitable VS results that ranged from 502.1 ± 36 to 665.1 ± 45 nm and high ZP values (≤ -41.4 ± 7.27 mV). Transmission electron microscopy revealed the spherical shape of the developed bilosomes. The in-vitro release study revealed prolonged release of rutin from bilosomes, relative to free drug. F2, prepared using the molar ratio span 60: cholesterol: sodium cholate 1:1:0.5, was selected for further investigations as it showed the highest EE%, smallest VS, optimum ZP, and persistent release profile. In-vivo studies were performed on drug-induced nephropathy in rats. Acute renal failure was induced using a single dose of potassium dichromate (PDC; 15 mg/kg; i.p). The selected formulation, F2, alleviated kidney dysfunction, oxidative stress and inflammation via decreasing MDA, TNF-α and TGF-β and increasing GSH. In addition, F2 promoted Akt/PI3K activation against PDC-induced acute renal failure. Histopathology results came in accordance with in-vivo results. Thus, bilosomes could be considered a potential delivery system for enhancing the oral delivery and kidney protection activity of rutin.

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