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Chitosan-coated taxifolin liposomes preserve renal structure and function in mice
Thaer A Altakhaineh1, Mohammad H Abukhalil2, Walhan Alshaer3
1Faculty of Pharmacy, Universiti Sultan Zainal Abidin, Besut Campus, Besut, Terengganu, Malaysia.
Abstract:
Isoproterenol (ISO), a nonselective β-adrenergic agonist, is widely used to induce myocardial injury and has been reported to cause secondary renal damage known as cardiorenal syndrome, partly driven by oxidative stress and inflammation. Taxifolin (TAX), a flavonoid with potent antioxidant and anti-inflammatory properties, is limited in clinical application due to poor solubility and low bioavailability. This study developed and evaluated chitosan-coated taxifolin liposomes (CS-TL) for the prevention of ISO-induced renal injury in mice. TAX liposomes (TL) were prepared via the ethanol injection method and coated with chitosan to obtain CS-TL. Physicochemical properties, including encapsulation efficiency (EE), particle size, and zeta potential, were characterized. Male mice pretreated with TL or CS-TL received ISO to induce cardiorenal damage. TL exhibited EE of 86.35 ± 3.15%, particle size of 154.8 ± 1.68 nm, and zeta potential of -32.54 ± 3.27 mV, while CS-TL demonstrated EE of 90.70 ± 1.47%, particle size of 289.4 ± 3.27 nm, and zeta potential of +35.26 ± 2.85 mV. ISO induced marked renal tissue damage, increased oxidative stress, inflammatory response, and apoptosis, and suppressed Nrf2/HO-1. Notably, CS-TL pretreatment markedly attenuated ISO-induced alterations in the aforementioned parameters and preserved renal histological architecture. These findings suggest that CS-TL could serve as a promising adjunctive therapeutic strategy for renoprotection in cardiorenal syndromes by ameliorating inflammation, oxidative stress, and apoptosis and restoring the Nrf2/HO-1 cascade.
Insights
Chitosan-coated taxifolin liposomes (CS-TL) show promise in preventing kidney damage caused by isoproterenol (ISO). CS-TL pretreatment protected against ISO-induced renal injury by reducing oxidative stress, inflammation, and apoptosis.
Area of Science:
- Pharmacology and Toxicology
- Nanomedicine
- Renal Physiology
Background:
- Isoproterenol (ISO) induces myocardial injury and cardiorenal syndrome, characterized by oxidative stress and inflammation.
- Taxifolin (TAX), an antioxidant and anti-inflammatory flavonoid, has limited clinical use due to poor solubility and bioavailability.
- Developing effective delivery systems for TAX is crucial for its therapeutic application in preventing organ damage.
Purpose of the Study:
- To develop and evaluate chitosan-coated taxifolin liposomes (CS-TL) for preventing isoproterenol-induced renal injury.
- To assess the physicochemical properties of taxifolin liposomes (TL) and CS-TL.
- To investigate the renoprotective effects of CS-TL against ISO-induced cardiorenal damage in mice.
Main Methods:
- Taxifolin liposomes (TL) were prepared using the ethanol injection method and subsequently coated with chitosan to form CS-TL.
- Physicochemical characterization included encapsulation efficiency (EE), particle size, and zeta potential measurements.
- Male mice were pretreated with TL or CS-TL before ISO administration to induce cardiorenal damage, followed by histological and biochemical analyses.
Main Results:
- TL exhibited an EE of 86.35%, particle size of 154.8 nm, and zeta potential of -32.54 mV.
- CS-TL showed improved EE (90.70%), larger particle size (289.4 nm), and a positive zeta potential (+35.26 mV).
- CS-TL pretreatment significantly attenuated ISO-induced renal damage, oxidative stress, inflammation, and apoptosis, while preserving renal histology and restoring the Nrf2/HO-1 pathway.
Conclusions:
- Chitosan-coated taxifolin liposomes (CS-TL) demonstrate enhanced physicochemical properties suitable for drug delivery.
- CS-TL effectively protects against isoproterenol-induced cardiorenal injury by mitigating oxidative stress, inflammation, and apoptosis.
- CS-TL represents a promising therapeutic strategy for renoprotection in cardiorenal syndromes, warranting further clinical investigation.
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