EVALUATION OF CARDIPROTECTIVE ACTIVITY OF RUTIN PHYTOSOME AGAINST DOXURUBICIN INDUCED CARDIOTOXICITY BY USING ANIMAL MODELS

Background: Doxorubicin remains a cornerstone anticancer agent, but its clinical utility is limited by dose-dependent cardiotoxicity mediated largely through oxidative stress and mitochondrial injury. Rutin, a flavonoid glycoside with well-documented antioxidant activity, is constrained therapeutically by poor aqueous solubility and limited membrane permeability. Complexation with phosphatidylcholine to form a phytosome was investigated as a strategy to overcome these limitations and enhance cardioprotective efficacy. Methods: Rutin phytosome was prepared by the thin-film hydration/solvent-evaporation technique at three rutin-to-phosphatidylcholine ratios (1:0.5, 1:1, 1:1.5) and characterised by entrapment efficiency, Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and in vitro dialysis-membrane drug release. The optimised formulation was evaluated in vivo in a five-group Wistar rat model of doxorubicin-induced cardiotoxicity (normal control; toxic control, doxorubicin 20 mg/kg i.p.; standard, carvedilol 30 mg/kg; test drug, rutin 50 mg/kg; test formulation, rutin phytosome 50 mg/kg), with cardiac biomarkers (CK-MB, LDH, troponin-I), myocardial antioxidant parameters (SOD, CAT, MDA), and histopathology as endpoints. Results: The 1:1 formulation (F2) gave the highest entrapment efficiency (94.2%). FTIR confirmed retention of rutin's characteristic bands with shifts indicative of hydrogen bonding, and SEM showed irregular, rough-surfaced, predominantly spherical particles. In vitro release was sustained, reaching 83.1% cumulative release at 6 hours. In vivo, doxorubicin produced marked elevation of CK-MB, LDH and troponin-I and depletion of SOD and CAT with elevated MDA, confirming cardiotoxicity. Pretreatment with rutin phytosome produced a greater reduction in all three cardiac biomarkers than plain rutin (CK-MB 34.14 ± 0.49 vs 38.68 ± 0.62 U/L; LDH 253.2 ± 3.83 vs 291.4 ± 3.97 IU/L; troponin-I 0.79 ± 0.037 vs 2.08 ± 0.020 ng/mL) and better restoration of antioxidant status, findings corroborated by graded histopathological recovery of myocardial architecture. Conclusion: Phospholipid complexation improved the physicochemical and biopharmaceutical profile of rutin and conferred superior protection against doxorubicin-induced cardiotoxicity relative to free rutin, supporting further pharmacokinetic and clinical translational evaluation of rutin phytosome as an adjuvant cardioprotective agent.