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

• Published in: Scientific reports Vol. 14; no. 1; pp. 23799 - 14
• Main Authors: Mohsen, Amira Mohamed, Wagdi, Marwa Anwar, Salama, Abeer
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; 639/925/352/152; 692/4022/1585; Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; Acute renal injury; Potassium dichromate; Akt/PI3K; Administration, Oral; AKT protein; Animals; Bilosomes; Bioavailability; Cholesterol; Glycosides; Histopathology; Humanities and Social Sciences; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidneys; Liposomes; Male; multidisciplinary; Nephropathy; Oxidative stress; Oxidative Stress - drug effects; Potassium; Potassium Dichromate; Rats; Rats, Wistar; Renal failure; Rutin; Rutin - administration & dosage; Rutin - chemistry; Rutin - pharmacology; Science; Science (multidisciplinary); Sodium cholate; Thin films; Transforming growth factor-b; Transmission electron microscopy; Tumor necrosis factor-α; Zeta potential; Rutin; Acute renal injury; Potassium dichromate; Akt/PI3K; Bilosomes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-73567-6

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. F 2 , 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.